{ "meta": { "api_version": "1.0.0", "dataset_version": "2.0.0", "corpus_snapshot": "2026-10-01T14:49:35+0200", "source_commit": "03bba2194c4832a1bcdfb704d54dd458ab0df021", "license": "CC-BY-4.0", "cite": "Barton O. Oliver's mTOR Atlas. doi:10.5281/zenodo.22059963", "docs": "https://mtor-atlas.org/api/" }, "count": 428, "data": [ { "sid": "DEM2016", "title": "Lysosomal recruitment of TSC2 is a universal response to cellular stress", "authors": "Demetriades C; Teleman AA et al.", "year": 2016, "journal": "Nature communications", "doi": "10.1038/ncomms10662", "pmid": "26868506", "pmcid": "PMC4754342", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Lysosomal recruitment of TSC2 is a universal response to cellular stress that inhibits mTORC1.", "url": "https://mtor-atlas.org/study/DEM2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEM2016.json" }, { "sid": "INOK2003", "title": "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling", "authors": "Inoki K; Guan KL et al.", "year": 2003, "journal": "Genes & development", "doi": "10.1101/gad.1110003", "pmid": "12869586", "pmcid": "PMC196227", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro; Drosophila", "peer_reviewed": true, "finding": "TSC2 is a GAP for Rheb; loss of TSC2 raises Rheb-GTP and constitutively activates mTOR.", "url": "https://mtor-atlas.org/study/INOK2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/INOK2003.json" }, { "sid": "INO2002", "title": "TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling", "authors": "Inoki K; Guan KL et al.", "year": 2002, "journal": "Nature Cell Biology", "doi": "10.1038/ncb839", "pmid": "12172553", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines", "peer_reviewed": true, "finding": "Akt directly phosphorylates and inactivates TSC2, disrupting the TSC1-TSC2 complex and releasing its inhibition of mTOR - the link between growth-factor/insulin signaling and mTORC1 activation.", "url": "https://mtor-atlas.org/study/INO2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/INO2002.json" }, { "sid": "YU2026", "title": "High-concentration hydrogen mitigates cognitive impairment in a murine model of Sepsis-associated encephalopathy by enhancing oligodendrocyte maturation and myelination in the mPFC", "authors": "Yu J; Qi W; Li F; Chang B; Wang Zengkun; Kan Y; Yu Yonghao; Yu Yang", "year": 2026, "journal": "Progress in Neuro-Psychopharmacology and Biological Psychiatry", "doi": "10.1016/j.pnpbp.2026.111892", "pmid": null, "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (CLP-induced SAE model)", "peer_reviewed": true, "finding": "In a mouse model of sepsis-associated encephalopathy (SAE), mTOR hyperactivation impairs oligodendrocyte maturation and causes cognitive deficits; hydrogen gas and rapamycin suppress mTOR, restore myelination, and improve cognition in these mice.", "url": "https://mtor-atlas.org/study/YU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/YU2026.json" }, { "sid": "JIN2026B", "title": "Rapamycin attenuates age-related atrial remodeling and fibrillation by targeting HIF-1α-mediated metabolic dysregulation.", "authors": "Jin L; Jiang T; Gong H et al.", "year": 2026, "journal": "Biochimica et Biophysica Acta - Molecular Basis of Disease", "doi": "10.1016/j.bbadis.2026.168438", "pmid": null, "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (D-galactose aging model)", "peer_reviewed": true, "finding": "Dietary rapamycin reduced aging-induced atrial fibrillation susceptibility and atrial remodelling in D-galactose-aged mice, acting through mTOR-independent inhibition of HIF-1α plus restored mitochondrial function and insulin sensitivity.", "url": "https://mtor-atlas.org/study/JIN2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/JIN2026B.json" }, { "sid": "LOF2011", "title": "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop", "authors": "Löffler AS et al.", "year": 2011, "journal": "Autophagy", "doi": "10.4161/auto.7.7.15451", "pmid": "21460634", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells; mouse", "peer_reviewed": true, "finding": "ULK1 phosphorylates and inhibits AMPK in return, showing autophagy signaling is a bidirectional feedback loop, not a one-way switch.", "url": "https://mtor-atlas.org/study/LOF2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/LOF2011.json" }, { "sid": "KIM2003", "title": "GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR", "authors": "Kim DH; Sarbassov DD; Ali SM; Latek RR; Guntur KVP; Erdjument-Bromage H; Tempst P; Sabatini DM", "year": 2003, "journal": "Molecular Cell", "doi": "10.1016/s1097-2765(03)00114-x", "pmid": "12718876", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (biochemistry)", "peer_reviewed": true, "finding": "Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex.", "url": "https://mtor-atlas.org/study/KIM2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2003.json" }, { "sid": "JIN2026C", "title": "Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice", "authors": "de Mol J; de Korte DH; Depuydt MAC; Smit V; Kleijn MNAB; van Santbrink PJ; Binder CJ; Porsch F; Schaftenaar FH; Foks AC", "year": 2026, "journal": "Aging Cell", "doi": "10.1111/acel.70730", "pmid": "42775680", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Aged (80-90 wk) male Ldlr-/- mice with established atherosclerosis; rapamycin i.p. triweekly x 8 weeks vs. control", "peer_reviewed": true, "finding": "In aged atherosclerotic mice, rapamycin (mTORC1 inhibition) reduced plaque macrophage content and total T cell numbers, shifted CD8 T cells from effector to central-memory phenotype, enriched aortic regulatory T cells (higher Foxp3/Tgfb1), reduced Tfh cells, germinal-center B cells, plasma cells and autoantibody levels, diminished age-associated B cells, and lowered senescence-enrichment scores in aortic leukocytes -- consistent with rapamycin acting as an immune-rejuvenation therapeutic that mitigates age-related atherogenic inflammation.", "url": "https://mtor-atlas.org/study/JIN2026C/", "api_url": "https://mtor-atlas.org/api/v1/studies/JIN2026C.json" }, { "sid": "LIS2026", "title": "Notoginsenoside R1 Alleviates Acetaminophen-Induced Liver Injury via MAPK/mTOR-Mediated Autophagy.", "authors": "Li S, Liu Z, Pan G, Li Y, Lv K", "year": 2026, "journal": "The American Journal of Chinese Medicine", "doi": "10.1142/S0192415X26500576", "pmid": "42459050", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Notoginsenoside R1 alleviates acetaminophen-induced acute liver injury by activating protective autophagy through MAPK/mTOR pathway modulation, reducing hepatocyte death and oxidative damage.", "url": "https://mtor-atlas.org/study/LIS2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIS2026.json" }, { "sid": "GWI2008", "title": "AMPK phosphorylation of raptor mediates a metabolic checkpoint", "authors": "Gwinn DM; Shackelford DB; Egan DF; Mihaylova MM; Mery A; Vasquez DS; Turk BE; Shaw RJ", "year": 2008, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2008.03.003", "pmid": "18439900", "pmcid": "PMC2674027", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human/mouse cells (biochemistry)", "peer_reviewed": true, "finding": "Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into.", "url": "https://mtor-atlas.org/study/GWI2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/GWI2008.json" }, { "sid": "VITTE2026", "title": "Efficacy and safety of everolimus in heart transplant recipients: A meta-analysis", "authors": "Vitte SH; Luna AM; Pille JJ; Pinheiro BN; Souza MBL; Irudhayaraj CDJ; Munaretto GM", "year": 2026, "journal": "JHLT Open", "doi": "10.1016/j.jhlto.2026.100610", "pmid": "42656203", "pmcid": "PMC13506258", "evidence": { "code": "S", "label": "Synthesis of human data", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (adult and paediatric heart transplant recipients)", "peer_reviewed": true, "finding": "Meta-analysis of 60 studies (1786 heart transplant recipients): everolimus-based immunosuppression reduced cardiac allograft vasculopathy progression on IVUS (RR ~0.57) and preserved renal function (eGFR +10-15 mL/min) when combined with calcineurin-inhibitor minimisation, with neutral all-cause mortality (RR ~0.98) but more adverse events and treatment discontinuation.", "url": "https://mtor-atlas.org/study/VITTE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/VITTE2026.json" }, { "sid": "VIL2021", "title": "mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis", "authors": "Villa E; Sahu U; O'Hara BP; Ali ES; Helmin KA; Asara JM; Gao P; Singer BD; Ben-Sahra I", "year": 2021, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2021.03.009", "pmid": "33756106", "pmcid": "PMC8141029", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells; mouse xenograft tumors", "peer_reviewed": true, "finding": "SAMTOR (GU2017) showed the cell can sense S-adenosylmethionine and report it to mTORC1. This study runs the arrow the other way: mTORC1 controls how much SAM the cell makes. Downstream of mTORC1, c-MYC binds intron 1 of MAT2A and raises expression of the enzyme that produces SAM, the cell's main methyl donor; mTORC1 separately increases the protein level of WTAP, the regulatory subunit of the m6A RNA methyltransferase complex. Together these raise m6A methylation of mRNA, which primes the translation machinery for growth. Blocking MAT2A lowers SAM, m6A, protein synthesis rate and tumor growth.", "url": "https://mtor-atlas.org/study/VIL2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/VIL2021.json" }, { "sid": "DEOLIVEIRA2026", "title": "Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16 oncogene expression in breast cancer.", "authors": "de Oliveira Isidio BE; Fontes PHB; da Silva GRP; Leao SL; de Franca Sao Marcos B; et al.", "year": 2026, "journal": "Exploration of targeted anti-tumor therapy", "doi": "10.37349/etat.2026.1002391", "pmid": "42558973", "pmcid": "PMC13439120", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human (clinical samples, FFPE tissue)", "peer_reviewed": true, "finding": "In breast tumour tissue (48 of 92 patients with usable RNA), HPV16 oncogene expression was associated with higher PI3K and lower mTOR transcript levels. The design is correlational and measures mRNA only, so it does not show that the virus activates the mTOR pathway.", "url": "https://mtor-atlas.org/study/DEOLIVEIRA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEOLIVEIRA2026.json" }, { "sid": "SIL2026", "title": "Enforcing mTORC1 activity in therapeutic CD4+ T cells promotes persistence but eventual immune exhaustion", "authors": "Sillito F; Armbrecht E; O'Neill AT; McIntyre A; Nyatondo M; Holler A; Callender LA; Henson SM; Stauss H; Chakraverty R", "year": 2026, "journal": "Journal of Immunology", "doi": "10.1093/jimmun/vkag206", "pmid": "42566506", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse CD4+ T cells, adoptive transfer tumor model", "peer_reviewed": true, "finding": "Enforced RHEB overexpression (mTORC1 hyperactivation) in therapeutic CD4+ T cells boosts initial proliferation/persistence after adoptive transfer, but drives cells toward an exhausted phenotype (co-inhibitory receptors, impaired re-proliferation on rechallenge) -- a double-edged sword for CAR/TCR-T cell engineering, distinct from the CD8 response to the same manipulation.", "url": "https://mtor-atlas.org/study/SIL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SIL2026.json" }, { "sid": "BRO1996", "title": "Dwarf mice and the ageing process", "authors": "Brown-Borg HM; Bartke A et al.", "year": 1996, "journal": "Nature", "doi": "10.1038/384033a0", "pmid": "8900272", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Ames dwarf mice (growth-hormone deficient)", "peer_reviewed": true, "finding": "Mice with growth hormone deficiency lived substantially longer than normal littermates - founding observation linking reduced growth-signaling to mammalian longevity.", "url": "https://mtor-atlas.org/study/BRO1996/", "api_url": "https://mtor-atlas.org/api/v1/studies/BRO1996.json" }, { "sid": "RIV2026", "title": "Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis", "authors": "Rivalta B; Maccari ME et al.", "year": 2026, "journal": "Journal of Allergy and Clinical Immunology", "doi": "10.1016/j.jaci.2026.09.014", "pmid": "42805311", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (retrospective multicenter registry, n=95 APDS patients)", "peer_reviewed": true, "finding": "In a 95-patient ESID registry of Activated PI3Kδ Syndrome (APDS), rapamycin and the targeted PI3Kδ inhibitor leniolisib produced comparable overall response rates for lymphoproliferation (67% vs 64%), but treatment-limiting adverse events occurred only in the rapamycin-treated group; lymphoma cases were observed during follow-up in the cohort.", "url": "https://mtor-atlas.org/study/RIV2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/RIV2026.json" }, { "sid": "KOR2011", "title": "Lysosomal positioning coordinates cellular nutrient responses", "authors": "Korolchuk VI; Saiki S; Lichtenberg M; Siddiqi FH; Roberts EA; Imarisio S; Jahreiss L; Sarkar S; Futter M; Menzies FM; O'Kane CJ; Deretic V; Rubinsztein DC", "year": 2011, "journal": "Nature cell biology", "doi": "10.1038/ncb2204", "pmid": "21394080", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Where the lysosome sits inside the cell helps decide whether mTORC1 is on. With nutrients available, lysosomes move to the cell periphery, physically close to the plasma-membrane signalling modules, and mTORC1 is active there; starvation changes intracellular pH and pulls lysosomes into a cluster around the nucleus, where mTORC1 output falls and autophagy is released. Lysosomal position also sets the rate of autophagosome-lysosome fusion, so one variable acts at both the initiation and the termination end of autophagic flux. This added a spatial axis to mTORC1 regulation that Rag/Ragulator recruitment alone does not account for.", "url": "https://mtor-atlas.org/study/KOR2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/KOR2011.json" }, { "sid": "HSI2012", "title": "The translational landscape of mTOR signalling steers cancer initiation and metastasis", "authors": "Hsieh AC; Liu Yi; Edlind MP; Ingolia NT; Janes MR; Sher A; et al.; Ruggero D", "year": 2012, "journal": "Nature", "doi": "10.1038/nature10912", "pmid": "22367541", "pmcid": "PMC3663483", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse models + human prostate cancer", "peer_reviewed": true, "finding": "Showed WHY mTOR-driven translation matters for cancer: in prostate cancer, oncogenic mTOR selectively translates a specific set of pro-invasion mRNAs that drive metastasis. An ATP-competitive mTOR inhibitor (INK128) reversed that signature - an early preclinical rationale from mouse models and cell lines, not a clinical result.", "url": "https://mtor-atlas.org/study/HSI2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/HSI2012.json" }, { "sid": "BOU2020", "title": "AIMTOR, a BRET biosensor for live imaging, reveals subcellular mTOR signaling and dysfunctions", "authors": "Bouquier N; Perroy J; Ollendorff V et al.", "year": 2020, "journal": "BMC Biology", "doi": "10.1186/s12915-020-00790-8", "pmid": "32620110", "pmcid": "PMC7334845", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "HEK293 cells; primary hippocampal neurons and muscle cells (mouse); biosensor tool", "peer_reviewed": true, "finding": "AIMTOR is a genetically encoded BRET biosensor that reads out mTOR activity live in single cells and in specific subcellular compartments (cytosol, lysosome surface, nucleus, near mitochondria).", "url": "https://mtor-atlas.org/study/BOU2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/BOU2020.json" }, { "sid": "CHEN2026C", "title": "Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation", "authors": "Chen Xianglong; Gao H; Wu W; Shi P; Chen Yuhang; Zhang A; Cheng Z; Wu W; Yu Z; Zhang Y", "year": 2026, "journal": "Advanced Science", "doi": "10.1002/advs.77428", "pmid": "42658647", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human nucleus pulposus cells; rat caudal needle-puncture model", "peer_reviewed": true, "finding": "Loss of chaperone-mediated autophagy lets its substrate midnolin (MIDN) accumulate; MIDN binds TSC2 and drives its proteasomal degradation independently of ubiquitination, de-repressing mTORC1 and causing senescence, SASP and matrix loss in disc cells. MIDN knockdown, LAMP2A overexpression or rapamycin each blocked the degeneration - a new upstream route to mTORC1 hyperactivation.", "url": "https://mtor-atlas.org/study/CHEN2026C/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHEN2026C.json" }, { "sid": "JAC2006", "title": "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity", "authors": "Jacinto E; Su B et al.", "year": 2006, "journal": "Cell", "doi": "10.1016/j.cell.2006.08.033", "pmid": "16962653", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SIN1 maintains rictor-mTOR integrity and confers mTORC2 Akt-Ser473 kinase activity and substrate specificity.", "url": "https://mtor-atlas.org/study/JAC2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/JAC2006.json" }, { "sid": "BOB2026", "title": "mTOR signaling in aging: from causality to geroprotective interventions and hallmark-level outcomes", "authors": "Bobok N", "year": 2026, "journal": "Aging (Albany NY)", "doi": "10.18632/aging.206423", "pmid": "42765942", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Narrative review synthesis (model organisms + human associative data)", "peer_reviewed": true, "finding": "Frames mTOR as a dynamic, context-dependent signaling hub integrating nutrient sensing, proteostasis, autophagy and stress adaptation across the hallmarks of aging; surveys geroprotective interventions (autophagy activation, dietary restriction, exercise, senotherapeutics) that partly converge on mTOR signaling. Causal evidence for mTOR in lifespan regulation is strong in model organisms; human data remain associative but biologically consistent.", "url": "https://mtor-atlas.org/study/BOB2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/BOB2026.json" }, { "sid": "ALI2020", "title": "ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis", "authors": "Ali ES; Sahu U; Villa E; O'Hara BP; Gao P; Beaudet C; Wood AW; Asara JM; Ben-Sahra I", "year": 2020, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2020.05.001", "pmid": "32485148", "pmcid": "PMC7306006", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cancer cells; tumor", "peer_reviewed": true, "finding": "The Atlas records several routes by which mTORC1 drives purine synthesis. This study shows mTORC1 is not the only growth pathway with that power: RAS-ERK signalling stimulates purine synthesis directly and within minutes, because ERK2 - but not ERK1 - phosphorylates the purine synthesis enzyme PFAS at Thr619. Cells expressing a PFAS that cannot be phosphorylated make fewer purines, form fewer colonies and grow smaller tumors. Two points bound the mTOR claim: the control is posttranslational, so it acts far faster than transcription or translation, and it is a parallel input, so purine synthesis in a RAS-driven tumor is not read out from mTORC1 activity alone.", "url": "https://mtor-atlas.org/study/ALI2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/ALI2020.json" }, { "sid": "CHI2012", "title": "Regulation and function of mTOR signalling in T cell fate decisions", "authors": "Chi H", "year": 2012, "journal": "Nature reviews. Immunology", "doi": "10.1038/nri3198", "pmid": "22517423", "pmcid": "PMC3417069", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of mTOR signalling in T-cell fate decisions.", "url": "https://mtor-atlas.org/study/CHI2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHI2012.json" }, { "sid": "CHEN2026", "title": "FGF21-modified adipose stem cell-derived exosomes promote wound healing by activating fibroblast glycolysis through AMPK/mTOR signaling.", "authors": "Chen K; Chen X; Wen C; Chen W; Liao Z; et al.", "year": 2026, "journal": "Cellular signalling", "doi": "10.1016/j.cellsig.2026.112742", "pmid": "42551612", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse + Human fibroblasts", "peer_reviewed": true, "finding": "FGF21-enriched exosomes from engineered ADSCs promote chronic wound healing by activating fibroblast glycolysis, with AMPK activated and mTOR signaling suppressed, improving proliferation, migration, and tissue repair in a mouse model.", "url": "https://mtor-atlas.org/study/CHEN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHEN2026.json" }, { "sid": "KRA2018", "title": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort", "authors": "Kraig E; Linehan LA; Liang H; Romo TQ; Liu Q; et al.; Kellogg DL", "year": 2018, "journal": "Experimental Gerontology", "doi": "10.1016/j.exger.2017.12.026", "pmid": "29408453", "pmcid": "PMC5869166", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, pilot RCT (n=25, ages 70-95)", "peer_reviewed": true, "finding": "A safety-first pilot RCT (n=25, ages 70-95) asking the basic question before any longevity trial: is daily rapamycin safe in healthy older people? Over 8+ weeks it was well tolerated with only minor red-blood-cell changes and - importantly - NO rise in blood glucose or insulin resistance in this short window. Groundwork for larger aging trials like PEARL.", "url": "https://mtor-atlas.org/study/KRA2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/KRA2018.json" }, { "sid": "XIA2026", "title": "Nutrient-sensing pathways in adult stem cells: Orchestrating homeostasis, aging, and disease", "authors": "Xiao T; Zeng YA; Hu C et al.", "year": 2026, "journal": "Seminars in Cell & Developmental Biology", "doi": "10.1016/j.semcdb.2026.103690", "pmid": "42546460", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (adult stem cells, multiple tissue systems)", "peer_reviewed": true, "finding": "Proposes an integrated framework in which mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling jointly govern adult stem cell transitions between quiescence, activation, and differentiation; age-related dysregulation of this nutrient-sensing network drives stem cell exhaustion and tissue degeneration, and interventions (mTOR inhibitors, AMPK activators, NAD+ precursors, dietary strategies) can restore ASC function.", "url": "https://mtor-atlas.org/study/XIA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/XIA2026.json" }, { "sid": "MAX2009", "title": "Molecular mechanisms of mTOR-mediated translational control", "authors": "Ma XM; Blenis J et al.", "year": 2009, "journal": "Nature reviews. Molecular cell biology", "doi": "10.1038/nrm2672", "pmid": "19339977", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of the molecular mechanisms of mTOR-mediated translational control.", "url": "https://mtor-atlas.org/study/MAX2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAX2009.json" }, { "sid": "HEI1991", "title": "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast", "authors": "Heitman J; Movva NR; Hall MN", "year": 1991, "journal": "Science", "doi": "10.1126/science.1715094", "pmid": "1715094", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast (Saccharomyces cerevisiae)", "peer_reviewed": true, "finding": "Discovery of the TOR1 and TOR2 genes in yeast as the targets whose disruption causes rapamycin's cell-cycle-arresting toxicity - the original genetic identification of the TOR pathway.", "url": "https://mtor-atlas.org/study/HEI1991/", "api_url": "https://mtor-atlas.org/api/v1/studies/HEI1991.json" }, { "sid": "GAO2026", "title": "Astragaloside IV Mitigates Tacrolimus-Induced Chronic Nephrotoxicity by Regulating the mTOR-TFEB-GADD45alpha Pathway", "authors": "Ping Gao, Xinwei Cheng, Rui Xu, Xinyu Huang, Jianqiao Wang, Maochang Liu, Xiuxun Wu, Xinlei Guan, Yunzhou Chen, Zhenpeng Qiu", "year": 2026, "journal": "Journal of Agricultural and Food Chemistry", "doi": "10.1021/acs.jafc.5c17921", "pmid": "42438242", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro (renal cell lines)", "peer_reviewed": true, "finding": "Astragaloside IV protects against tacrolimus-induced nephrotoxicity by inhibiting mTOR to activate TFEB and restore autophagy, nominating the mTOR-TFEB-GADD45alpha axis as a calcineurin-independent candidate therapeutic target (preclinical; no human data) in TICN.", "url": "https://mtor-atlas.org/study/GAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAO2026.json" }, { "sid": "FON2010", "title": "Extending healthy life span--from yeast to humans", "authors": "Fontana L; Partridge L; Longo VD", "year": 2010, "journal": "Science", "doi": "10.1126/science.1172539", "pmid": "20395504", "pmcid": "PMC3607354", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (yeast to humans)", "peer_reviewed": true, "finding": "Influential review proposing that dietary restriction and reduced nutrient-sensing signalling (mTOR, GH/IGF-1) may slow ageing through similar, evolutionarily conserved mechanisms. Lifespan extension is shown in yeast, invertebrates, rodents and rhesus monkeys; in humans the evidence is limited to protective biomarker changes and genetic associations.", "url": "https://mtor-atlas.org/study/FON2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/FON2010.json" }, { "sid": "CAS2009", "title": "mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging", "authors": "Castilho RM; Gutkind JS et al.", "year": 2009, "journal": "Cell stem cell", "doi": "10.1016/j.stem.2009.06.017", "pmid": "19733540", "pmcid": "PMC2939833", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Wnt-induced mTOR activation drives epidermal stem-cell senescence; rapamycin rescues it.", "url": "https://mtor-atlas.org/study/CAS2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAS2009.json" }, { "sid": "SAC2011", "title": "Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size", "authors": "Saci A; Carpenter CL et al.", "year": 2011, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2011.03.017", "pmid": "21474067", "pmcid": "PMC3750737", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Rac1 binds and regulates both mTORC1 and mTORC2, controlling their localization and cell growth.", "url": "https://mtor-atlas.org/study/SAC2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAC2011.json" }, { "sid": "FER2024", "title": "Spatial and functional separation of mTORC1 signalling in response to different amino acid sources", "authors": "Fernandes SA; Angelidaki DD; Nüchel J; Pan J; Gollwitzer P; Elkis Y; Artoni F; Wilhelm S; Kovacevic-Sarmiento M; Demetriades C", "year": 2024, "journal": "Nature Cell Biology", "doi": "10.1038/s41556-024-01523-7", "pmid": "39385049", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (HEK293)", "peer_reviewed": true, "finding": "mTORC1 regulation and downstream substrate phosphorylation are spatially separated: lysosomal mTORC1 (fed by local lysosomal proteolysis) and cytoplasmic mTORC1 (fed by exogenous amino acids) phosphorylate distinct substrates depending on amino acid source, challenging the single lysosomal-hub model.", "url": "https://mtor-atlas.org/study/FER2024/", "api_url": "https://mtor-atlas.org/api/v1/studies/FER2024.json" }, { "sid": "WOL2015", "title": "Sestrin2 is a leucine sensor for the mTORC1 pathway", "authors": "Wolfson RL; Sabatini DM et al.", "year": 2015, "journal": "Science", "doi": "10.1126/science.aab2674", "pmid": "26449471", "pmcid": "PMC4698017", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1.", "url": "https://mtor-atlas.org/study/WOL2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/WOL2015.json" }, { "sid": "OKA2013", "title": "Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma", "authors": "Okazaki H; Matsunaga N; Fujioka T; Okazaki F; Akagawa Y; Tsurudome Y; Ono M; Kuwano M; Koyanagi S; Ohdo S", "year": 2013, "journal": "Cancer Research", "doi": "10.1158/0008-5472.CAN-12-3241", "pmid": "24253377", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "RenCa tumour-bearing mice; NIH 3T3 cells", "peer_reviewed": true, "finding": "In mouse kidney tumours, active phosphorylated mTOR and total mTOR protein followed a 24-hour rhythm, set by the clock through the ubiquitin ligase Fbxw7. Giving everolimus when mTOR was high improved survival compared with other dosing times. Same drug, same dose - the clock time of dosing changed the outcome.", "url": "https://mtor-atlas.org/study/OKA2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/OKA2013.json" }, { "sid": "BO2026", "title": "Molecular and metabolic dysregulation of lung cancer in developing anti-tumor activity by gambogic acid mediated mTOR signaling: in vitro and computational study.", "authors": "Bo S, Liao Y, Chen X, Liu C, Pang J", "year": 2026, "journal": "3 Biotech", "doi": "10.1007/s13205-026-04938-1", "pmid": "42459409", "pmcid": "PMC13369087", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human lung cancer cell lines", "peer_reviewed": true, "finding": "Computational (network pharmacology and docking) plus in vitro study: gambogic acid is cytotoxic and pro-apoptotic in A549 lung cancer cells and docks most strongly to AKT and the mTOR effector S6K1 (RPS6KB1). Direct mTOR kinase inhibition was not measured; no in vivo or human data.", "url": "https://mtor-atlas.org/study/BO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/BO2026.json" }, { "sid": "YIN2026", "title": "Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1)", "authors": "Yin J; Yang M et al.", "year": 2026, "journal": "Nature Communications", "doi": "10.1038/s41467-026-75306-z", "pmid": "42414312", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Recombinant human protein (cryo-EM)", "peer_reviewed": true, "finding": "Cryo-EM structures of human PAT1 (SLC36A1) in apo and substrate-bound states reveal a convergent binding mode for diverse zwitterionic amino acids. This is a structural study; PAT1's role in lysosomal amino acid export and mTORC1 activation comes from earlier work.", "url": "https://mtor-atlas.org/study/YIN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/YIN2026.json" }, { "sid": "MIAO2026", "title": "Chronic Kidney Disease Risk Posed by 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) Benzene (EDPrB): An AOP of mTOR-Mediated Autophagy Dysregulation.", "authors": "Miao C; Zhang B; Yu W; Li Y; Cao Z", "year": 2026, "journal": "Environmental science & technology", "doi": "10.1021/acs.est.6c06697", "pmid": null, "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse (Kunming) + HK-2 human cell line", "peer_reviewed": true, "finding": "In mice, the environmental pollutant EDPrB accumulates in the kidney and causes CKD via mTOR hyperactivation, leading to autophagy dysregulation, inflammation and fibrosis; rapamycin rescue identified mTOR as the molecular initiating event, with corroborating data in HK-2 human kidney cells.", "url": "https://mtor-atlas.org/study/MIAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MIAO2026.json" }, { "sid": "JEW2015", "title": "Metabolism. Differential regulation of mTORC1 by leucine and glutamine", "authors": "Jewell JL; Guan KL et al.", "year": 2015, "journal": "Science", "doi": "10.1126/science.1259472", "pmid": "25567907", "pmcid": "PMC4384888", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Glutamine activates mTORC1 via a Rag-independent, Arf1-dependent route distinct from leucine.", "url": "https://mtor-atlas.org/study/JEW2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/JEW2015.json" }, { "sid": "BCH2026", "title": "Rapamycin-induced fatty liver in mice is attenuated by chloroquine co-treatment in an ERRα-dependent manner", "authors": "B'chir W; Giguère V et al.", "year": 2026, "journal": "Journal of Endocrinology", "doi": "10.1530/JOE-26-0176", "pmid": "42544714", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Side effect", "model_system": "Mouse (rapamycin-induced MASLD model; ERRα-null mice)", "peer_reviewed": true, "finding": "Chloroquine co-treatment attenuates rapamycin-induced hepatic steatosis (a known mTORC1-inhibitor side effect) in mice, and this rescue depends on the nuclear receptor ERRα; RNA-seq shows chloroquine reverses rapamycin-driven upregulation of lipid-metabolism genes, with ERRα identified as a top transcriptional regulator of the effect.", "url": "https://mtor-atlas.org/study/BCH2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/BCH2026.json" }, { "sid": "ZHO2001", "title": "Role of AMP-activated protein kinase in mechanism of metformin action", "authors": "Zhou G et al.", "year": 2001, "journal": "J Clin Invest", "doi": "10.1172/JCI13505", "pmid": "11602624", "pmcid": "PMC209533", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Rat; hepatocytes; skeletal muscle", "peer_reviewed": true, "finding": "Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis.", "url": "https://mtor-atlas.org/study/ZHO2001/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHO2001.json" }, { "sid": "SZW2021", "title": "Regulation and metabolic functions of mTORC1 and mTORC2", "authors": "Szwed A; Jacinto E et al.", "year": 2021, "journal": "Physiological reviews", "doi": "10.1152/physrev.00026.2020", "pmid": "33599151", "pmcid": "PMC8424549", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Comprehensive review of the regulation and metabolic functions of mTORC1 and mTORC2.", "url": "https://mtor-atlas.org/study/SZW2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/SZW2021.json" }, { "sid": "ARR2015", "title": "Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system", "authors": "Arriola Apelo SI; Lamming DW et al.", "year": 2015, "journal": "Aging cell", "doi": "10.1111/acel.12405", "pmid": "26463117", "pmcid": "PMC4717280", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Intermittent rapamycin regimens (weekly, or every 5 days) largely spared glucose tolerance, pyruvate tolerance, fasting glucose and insulin, beta-cell function and the immune system, while still inhibiting mTORC1 -- unlike daily dosing, which impaired all of them. IMPORTANT SCOPE: this study measured side effects only. It did NOT measure lifespan or any other benefit endpoint, so it shows the harm can be reduced, not that the benefit is retained. For evidence that a non-continuous schedule preserves a survival benefit, see BIT2016.", "url": "https://mtor-atlas.org/study/ARR2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/ARR2015.json" }, { "sid": "GOU2023", "title": "The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease", "authors": "Goul C; Zoncu R et al.", "year": 2023, "journal": "Nature reviews. Molecular cell biology", "doi": "10.1038/s41580-023-00641-8", "pmid": "37612414", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Authoritative review of the molecular basis of nutrient sensing and signalling by mTORC1 in disease.", "url": "https://mtor-atlas.org/study/GOU2023/", "api_url": "https://mtor-atlas.org/api/v1/studies/GOU2023.json" }, { "sid": "EFE2012", "title": "Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival", "authors": "Efeyan A; Sabatini DM et al.", "year": 2012, "journal": "Nature", "doi": "10.1038/nature11745", "pmid": "23263183", "pmcid": "PMC4000705", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (RagA GTP knock-in)", "peer_reviewed": true, "finding": "Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting.", "url": "https://mtor-atlas.org/study/EFE2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/EFE2012.json" }, { "sid": "HAR2004", "title": "The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins", "authors": "Harrington LS; Findlay GM; Lamb RF et al.", "year": 2004, "journal": "The Journal of Cell Biology", "doi": "10.1083/jcb.200403069", "pmid": "15249583", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells (TSC1/TSC2-null MEFs, human cells)", "peer_reviewed": true, "finding": "One of two 2004 papers that placed mTORC1's main negative feedback loop downstream of TSC-Rheb-S6K1 (rapamycin-sensitive IRS-1 degradation had been reported earlier, Haruta 2000). When mTORC1/S6K1 activity is left switched on, S6K1 phosphorylates IRS-1 and represses its expression, so the insulin receptor can no longer signal to PI3K. This is the textbook explanation for why blocking mTORC1 paradoxically raises Akt activity, and it contributes to insulin resistance when mTORC1 is chronically overactive (for example with TSC loss or nutrient excess). The insulin resistance seen with chronic rapamycin is instead attributed mainly to mTORC2 disruption (LAM2012).", "url": "https://mtor-atlas.org/study/HAR2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAR2004.json" }, { "sid": "MAN2014", "title": "mTOR inhibition improves immune function in the elderly", "authors": "Mannick JB et al.", "year": 2014, "journal": "Science Translational Medicine", "doi": "10.1126/scitranslmed.3009892", "pmid": "25540326", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, RCT, older adults", "peer_reviewed": true, "finding": "Low-dose everolimus improved influenza vaccine response by ~20% and reduced PD-1 expression on T lymphocytes.", "url": "https://mtor-atlas.org/study/MAN2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAN2014.json" }, { "sid": "HUA2013", "title": "mTORC2 controls actin polymerization required for consolidation of long-term memory", "authors": "Huang W; Zhu PJ; Zhang S; Zhou H; Stoica L; Galiano M; Krnjevic K; Roman G; Costa-Mattioli M", "year": 2013, "journal": "Nature Neuroscience", "doi": "10.1038/nn.3351", "pmid": "23455608", "pmcid": "PMC3615448", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Conditional Rictor-knockout mice (postnatal forebrain) and Drosophila", "peer_reviewed": null, "finding": "Conditional deletion of Rictor in the postnatal mouse forebrain reduced mTORC2 activity and selectively impaired long-term memory and the late phase of hippocampal LTP, with a comparable long-term-memory deficit in dTORC2-deficient flies. Hippocampal actin polymerisation was reduced, and restoring it rescued both L-LTP and long-term memory; a compound that raised mTORC2 activity converted early LTP into late LTP and enhanced memory. This is the loss-of-function AND rescue evidence that mTORC2 is required for memory consolidation - the arm chronic rapamycin also disrupts, and the study Open Question H8 needs for its mTORC2 liability leg, which until 2026-09-05 rested on no supporting study at all.", "url": "https://mtor-atlas.org/study/HUA2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/HUA2013.json" }, { "sid": "GUR2017", "title": "mTORC2 Promotes Tumorigenesis via Lipid Synthesis", "authors": "Guri Y; Hall MN et al.", "year": 2017, "journal": "Cancer cell", "doi": "10.1016/j.ccell.2017.11.011", "pmid": "29232555", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse; cells", "peer_reviewed": true, "finding": "mTORC2 promotes tumorigenesis through control of de novo lipid synthesis.", "url": "https://mtor-atlas.org/study/GUR2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUR2017.json" }, { "sid": "CHU1992", "title": "Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases", "authors": "Chung J; Blenis J et al.", "year": 1992, "journal": "Cell", "doi": "10.1016/0092-8674(92)90643-q", "pmid": "1377606", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "T cells; in vitro", "peer_reviewed": true, "finding": "Rapamycin-FKBP12 complex blocks growth-factor activation of p70 S6 kinase, linking the drug to a specific mitogenic pathway.", "url": "https://mtor-atlas.org/study/CHU1992/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHU1992.json" }, { "sid": "SCI2014", "title": "Mammalian target of rapamycin signaling in cardiac physiology and disease", "authors": "Sciarretta S; Sadoshima J et al.", "year": 2014, "journal": "Circulation research", "doi": "10.1161/CIRCRESAHA.114.302022", "pmid": "24481845", "pmcid": "PMC3995130", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of mTOR signalling in cardiac physiology and disease.", "url": "https://mtor-atlas.org/study/SCI2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/SCI2014.json" }, { "sid": "WANG2026", "title": "Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells", "authors": "Wang J; Ni Z; Zhang Xinxin; He L; Cheng X; Huang L; Ye H; Li P; Zhao TJ; Du X", "year": 2026, "journal": "Proceedings of the National Academy of Sciences", "doi": "10.1073/pnas.2601318123", "pmid": "42647134", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse T cells (conditional VPS18 / VPS11 knockout, in vitro and in vivo)", "peer_reviewed": true, "finding": "Identifies the CORVET and HOPS endolysosomal tethering complexes as upstream suppliers of intracellular amino acids in activated T cells, acquired via macropinocytosis. Loss of the core subunits VPS18 or VPS11 starves the cell of amino acids, switches on the integrated stress response and shuts down mTORC1; enforced mTORC1 activity rescues the proliferative defect while BIM deletion rescues survival, separating the two failure modes. Places vesicular nutrient acquisition upstream of the canonical lysosomal amino-acid-sensing arm of mTORC1.", "url": "https://mtor-atlas.org/study/WANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/WANG2026.json" }, { "sid": "XIE2026", "title": "Glutamine alleviates bisphenol A-induced jejunal injury in piglets involving mitochondrial function restoration and AMPK-mTOR signaling regulation.", "authors": "Xie J; Liu Z; Liu W et al.", "year": 2026, "journal": "Ecotoxicology and Environmental Safety", "doi": "10.1016/j.ecoenv.2026.120698", "pmid": "42660031", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Piglet; porcine intestinal epithelial cells", "peer_reviewed": true, "finding": "Glutamine supplementation alleviated bisphenol A-induced jejunal injury in piglets, restoring mitochondrial energy metabolism and barrier integrity alongside modulation of AMPK-mTOR signalling.", "url": "https://mtor-atlas.org/study/XIE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/XIE2026.json" }, { "sid": "WALTER2026", "title": "[Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial.", "authors": "Walter T; Jann H; Ansquer C; Deshayes E; Garcia-Carbonero R; Teule A et al.", "year": 2026, "journal": "Lancet", "doi": "10.1016/S0140-6736(26)00604-5", "pmid": "42392118", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human RCT", "peer_reviewed": true, "finding": "Phase 3 open-label RCT (n=309, 2:1): 177Lu-edotreotide gave longer PFS than everolimus (23.9 vs 14.1 months; HR 0.67) with fewer grade 3-4 treatment-related adverse events (18% vs 40%), supporting PRRT in early lines for progressive SSTR-positive GEP-NETs.", "url": "https://mtor-atlas.org/study/WALTER2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/WALTER2026.json" }, { "sid": "YAO2026", "title": "Salvianolic Acid B Enhances Motor Function Recovery after Spinal Cord Injury in Association with AKT/mTOR/HIF-1α Pathway Activation and Angiogenesis.", "authors": "Yao J; Chen Yingfeng; Pan F; Zhang S", "year": 2026, "journal": "Biological & Pharmaceutical Bulletin", "doi": "10.1248/bpb.b26-00280", "pmid": "42649073", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat (spinal cord injury model)", "peer_reviewed": true, "finding": "Salvianolic acid B improved motor recovery, neuronal survival and angiogenesis after rat spinal cord injury in association with AKT/mTOR/HIF-1α activation; the effects were reversed by the AKT inhibitor capivasertib.", "url": "https://mtor-atlas.org/study/YAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAO2026.json" }, { "sid": "CUI2026", "title": "Forsythoside A Alleviates Hypertensive Nephropathy by Promoting Mitophagy and Inhibiting Ferroptosis via ASCL1-CCNB1/mTOR Pathway.", "authors": "Cui X; Yang D; Zhang Z et al.", "year": 2026, "journal": "Journal of Ethnopharmacology", "doi": "10.1016/j.jep.2026.122346", "pmid": "42665168", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "C57BL/6 mouse; NRK-52E rat kidney cells", "peer_reviewed": true, "finding": "Forsythoside A binds ASCL1 and blocks the downstream CCNB1/mTOR axis, promoting mitophagy and suppressing ferroptosis to protect against Ang II-induced hypertensive nephropathy in mice — without lowering blood pressure.", "url": "https://mtor-atlas.org/study/CUI2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/CUI2026.json" }, { "sid": "BEN2008", "title": "Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy", "authors": "Bentzinger CF; Rueegg MA et al.", "year": 2008, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2008.10.002", "pmid": "19046572", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (muscle raptor/rictor KO)", "peer_reviewed": true, "finding": "In mice, muscle-specific raptor loss (not rictor) causes dystrophy, showing mTORC1 is essential for muscle homeostasis.", "url": "https://mtor-atlas.org/study/BEN2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/BEN2008.json" }, { "sid": "SAB1994", "title": "RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs", "authors": "Sabatini DM et al.", "year": 1994, "journal": "Cell", "doi": "10.1016/0092-8674(94)90570-3", "pmid": "7518356", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Rat brain (protein purification)", "peer_reviewed": true, "finding": "Discovery of the protein RAFT1 (today's mTOR) as the direct target of the FKBP12-rapamycin complex; one of three 1994 reports (with Brown et al. and Chiu et al.) that identified mammalian TOR, three years after TOR was found in yeast.", "url": "https://mtor-atlas.org/study/SAB1994/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAB1994.json" }, { "sid": "UMX2004", "title": "Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity", "authors": "Um SH; Thomas G et al.", "year": 2004, "journal": "Nature", "doi": "10.1038/nature02866", "pmid": "15306821", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (S6K1 KO)", "peer_reviewed": true, "finding": "S6K1 deletion protects mice from age- and diet-induced obesity and enhances insulin sensitivity.", "url": "https://mtor-atlas.org/study/UMX2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/UMX2004.json" }, { "sid": "SAR2006", "title": "Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB", "authors": "Sarbassov DD; Ali SM; Sengupta S; Sheen JH; Hsu PP; Bagley AF; Markhard AL; Sabatini DM", "year": 2006, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2006.03.029", "pmid": "16603397", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Multiple human/mouse cell lines", "peer_reviewed": true, "finding": "The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but LONG-term treatment also strips down mTORC2 in many cells, cutting Akt signaling. This is the mechanistic root of the insulin-resistance side effect later shown in mice (see Lamming 2012) - crucial for anyone dosing rapamycin for longevity.", "url": "https://mtor-atlas.org/study/SAR2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAR2006.json" }, { "sid": "EVA2026", "title": "PTEN regulates microtubule polymerization via mTORC2, but not mTORC1, in peripheral sensory neurons", "authors": "Evans S; Reglewski J; Rose H; Lewis C; Nayak A; Minsky C; McNeil E; Knowles B; Wang W; Li M; Luikart BW; Hong J", "year": 2026, "journal": "eNeuro", "doi": "10.1523/ENEURO.0116-26.2026", "pmid": "42642329", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse peripheral sensory neuron cultures (Pten-KO with Raptor or Rictor co-deletion, both sexes)", "peer_reviewed": true, "finding": "Uses Raptor (mTORC1) versus Rictor (mTORC2) co-deletion on a Pten-knockout background to ask which complex carries the growth signal to the microtubule cytoskeleton. Suppressing mTORC2 — but not mTORC1 — returns the accelerated microtubule polymerisation and neuronal hypertrophy of Pten-KO neurons to wild-type levels, and the effect is confined to the axonal growth cone rather than the proximal axon shaft. A clean genetic dissection on the comparatively thin mTORC2 side of the pathway.", "url": "https://mtor-atlas.org/study/EVA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/EVA2026.json" }, { "sid": "GUR2016", "title": "mTOR Signaling Confers Resistance to Targeted Cancer Drugs", "authors": "Guri Y; Hall MN et al.", "year": 2016, "journal": "Trends in cancer", "doi": "10.1016/j.trecan.2016.10.006", "pmid": "28741507", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of how mTOR signalling confers resistance to targeted cancer therapies.", "url": "https://mtor-atlas.org/study/GUR2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUR2016.json" }, { "sid": "MOR2013", "title": "mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation", "authors": "Morita M; Sonenberg N et al.", "year": 2013, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2013.10.001", "pmid": "24206664", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1 controls mitochondrial biogenesis and activity through 4E-BP-dependent translation.", "url": "https://mtor-atlas.org/study/MOR2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/MOR2013.json" }, { "sid": "FEL2009", "title": "Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2", "authors": "Feldman ME; Apsel B; Uotila A; Loewith R; Knight ZA; Ruggero D; Shokat KM", "year": 2009, "journal": "PLoS Biology", "doi": "10.1371/journal.pbio.1000038", "pmid": "19209957", "pmcid": "PMC2637922", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse fibroblasts + primary cells", "peer_reviewed": true, "finding": "The parallel discovery to Thoreen 2009 (same year), from the Shokat lab. Their TORKinibs (PP242, PP30) block mTOR's active site, hitting both complexes and shutting down cap-dependent translation that rapamycin misses. Together these two papers established a whole new drug class beyond rapamycin.", "url": "https://mtor-atlas.org/study/FEL2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/FEL2009.json" }, { "sid": "IYE2012", "title": "Genome sequencing identifies a basis for everolimus sensitivity", "authors": "Iyer G; Solit DB et al.", "year": 2012, "journal": "Science", "doi": "10.1126/science.1226344", "pmid": "22923433", "pmcid": "PMC3633467", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (patient) + sequencing", "peer_reviewed": true, "finding": "Genome sequencing of a single exceptional everolimus responder implicates TSC1 loss as the sensitivity basis. An n-of-1 observation, hypothesis-generating rather than confirmatory.", "url": "https://mtor-atlas.org/study/IYE2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/IYE2012.json" }, { "sid": "HOL2005", "title": "mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events", "authors": "Holz MK; Blenis J et al.", "year": 2005, "journal": "Cell", "doi": "10.1016/j.cell.2005.10.024", "pmid": "16286006", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTOR and S6K1 dynamically assemble the translation preinitiation complex on eIF3.", "url": "https://mtor-atlas.org/study/HOL2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/HOL2005.json" }, { "sid": "EGA2010", "title": "Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy", "authors": "Egan DF; Shaw RJ et al.", "year": 2010, "journal": "Science", "doi": "10.1126/science.1196371", "pmid": "21205641", "pmcid": "PMC3030664", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "AMPK directly phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy, opposing mTOR.", "url": "https://mtor-atlas.org/study/EGA2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/EGA2010.json" }, { "sid": "SRI2026", "title": "Nutrient/TOR signaling controls adipose mitochondrial transcription factor A (TFAM) to regulate organismal growth in Drosophila", "authors": "Sriskanthadevan-Pirahas S et al.", "year": 2026, "journal": "FEBS Lett", "doi": "10.1002/1873-3468.70427", "pmid": "42572502", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila (larvae, fat body)", "peer_reviewed": true, "finding": "In Drosophila larvae, nutrient/TOR signaling in the fat body (a key nutrient-sensing tissue) post-transcriptionally suppresses the mitochondrial transcription factor TFAM, and this TOR→TFAM axis in fat-body tissue controls whole-body developmental growth — a mechanistic link between nutrient sensing and interorgan growth control via mitochondrial bioenergetics.", "url": "https://mtor-atlas.org/study/SRI2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SRI2026.json" }, { "sid": "VER2026", "title": "Testosterone propionate maintains autophagic flux and mitochondrial integrity via regulation of the LC3B/p62/Beclin-1/mTOR axis in induced liver fibrosis.", "authors": "Verma S, Vaishnav S, Yadav M, Verma A, Washimkar K", "year": 2026, "journal": "Journal of Molecular Histology", "doi": "10.1007/s10735-026-10905-0", "pmid": "42461311", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat", "peer_reviewed": true, "finding": "Testosterone propionate protects against CCl4-induced liver fibrosis by maintaining mTOR-regulated autophagic flux via the LC3B/p62/Beclin-1 axis, preserving mitochondrial integrity; castration worsens fibrosis by impairing this pathway.", "url": "https://mtor-atlas.org/study/VER2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/VER2026.json" }, { "sid": "LIU2015", "title": "PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex", "authors": "Liu P; Wei W et al.", "year": 2015, "journal": "Cancer discovery", "doi": "10.1158/2159-8290.CD-15-0460", "pmid": "26293922", "pmcid": "PMC4631654", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "PIP3 relieves SIN1 PH-domain autoinhibition to activate the mTORC2 kinase complex.", "url": "https://mtor-atlas.org/study/LIU2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIU2015.json" }, { "sid": "LIST2026", "title": "Growth Hormone Receptor Antagonism Extends Lifespan", "authors": "List EO; Berryman DE; Lach GS; Minto DF; Weese K; Kopchick JJ", "year": 2026, "journal": "Aging cell", "doi": "10.1111/acel.70697", "pmid": "42701998", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "GHA transgenic mice expressing the bovine GH G119K receptor antagonist (line maintained since 1991), both sexes; independent 2-year-old frailty cohort", "peer_reviewed": true, "finding": "Transgenic expression of a growth hormone receptor antagonist — the G119K mutant chemistry behind the FDA-approved drug Pegvisomant — significantly extended both median and maximal lifespan in male (p = 0.044; p = 0.0037) and female mice, with maximal lifespan extended by 186 and 265 days respectively. Two-year-old antagonist mice were less frail and had greater grip strength despite increased adiposity. This is the first demonstration that antagonising GH action (as opposed to congenital GH deficiency, as in Ames/Snell dwarfs) extends mammalian lifespan — the GH/IGF-1 axis sits upstream of PI3K-Akt-mTOR, which is why it belongs in this corpus.", "url": "https://mtor-atlas.org/study/LIST2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIST2026.json" }, { "sid": "MAN2021", "title": "Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials", "authors": "Mannick JB; Teo G; Bernardo P; Quinn D; Russell K; Klickstein L; Marshall W; Shergill S", "year": 2021, "journal": "Lancet Healthy Longevity", "doi": "10.1016/S2666-7568(21)00062-3", "pmid": "33977284", "pmcid": "PMC8102040", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Negative_result", "model_system": "Humans, phase 2b + phase 3 RCT (n=1024 phase 3)", "peer_reviewed": true, "finding": "The crucial reality check. After the promising phase 2a, the large phase 3 trial (n=1024) FAILED its primary endpoint - RTB101 did not reduce clinically symptomatic respiratory illness (26% vs 25%, p=0.65). It still reliably switched on antiviral genes, so the biomarker moved but the clinical outcome did not. A textbook lesson that a promising biomarker is not a proven benefit.", "url": "https://mtor-atlas.org/study/MAN2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAN2021.json" }, { "sid": "JOS2024", "title": "mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction", "authors": "Joshi JN; Valvezan AJ et al.", "year": 2024, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2024.114543", "pmid": "39067023", "pmcid": "PMC12730006", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human and mouse cell lines (synchronised populations; fixed-cell single-cell imaging)", "peer_reviewed": true, "finding": "mTORC1 activity oscillates across the cell cycle (lowest in mitosis/G1, highest in S/G2) via the TSC complex, independent of Akt/Mek-Erk; low mTORC1 in G1 sensitizes cells to autophagy induction from the same partial inhibition or nutrient drop -- direct evidence that the TIMING/pattern of mTORC1 activity, not just its average level, shapes autophagy outcome.", "url": "https://mtor-atlas.org/study/JOS2024/", "api_url": "https://mtor-atlas.org/api/v1/studies/JOS2024.json" }, { "sid": "AWARE2026", "title": "Rapamycin increases cerebral blood flow and modulates metabolic, inflammatory, and microbiome profiles in healthy middle-aged APOE4 carriers: a pilot single-arm trial.", "authors": "Aware C; Neher CM; Woods C; Khegai O; Dwivedi AK; et al.; Lin AL", "year": 2026, "journal": "Journal of Cerebral Blood Flow and Metabolism", "doi": "10.1177/0271678X261490342", "pmid": "42723264", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human pilot single-arm trial, healthy middle-aged APOE4 carriers vs non-carriers", "peer_reviewed": true, "finding": "Single-arm pilot trial: 1 mg/day rapamycin for 4 weeks in 23 cognitively normal adults aged 45 to 65. Cerebral blood flow rose by more than 15% across several brain regions in the nine APOE4 carriers, while non-carriers showed no significant change; metabolic and inflammatory profiles improved and the gut microbiome was modulated. Uncontrolled, small and genotype-specific, so this is early evidence only.", "url": "https://mtor-atlas.org/study/AWARE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/AWARE2026.json" }, { "sid": "SAN2008", "title": "The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1", "authors": "Sancak Y; Sabatini DM et al.", "year": 2008, "journal": "Science", "doi": "10.1126/science.1157535", "pmid": "18497260", "pmcid": "PMC2475333", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines", "peer_reviewed": true, "finding": "Identifies the Rag GTPase family as the missing link that lets mTORC1 sense amino acids by controlling whether mTOR is positioned near its activator Rheb.", "url": "https://mtor-atlas.org/study/SAN2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAN2008.json" }, { "sid": "ORE2006", "title": "mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt", "authors": "O'Reilly KE; Rosen N et al.", "year": 2006, "journal": "Cancer research", "doi": "10.1158/0008-5472.CAN-05-2925", "pmid": "16452206", "pmcid": "PMC3193604", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells", "peer_reviewed": true, "finding": "mTORC1 inhibition relieves feedback and activates upstream RTK-PI3K-Akt signalling.", "url": "https://mtor-atlas.org/study/ORE2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/ORE2006.json" }, { "sid": "LAW2019", "title": "Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex", "authors": "Lawrence RE; Zoncu R et al.", "year": 2019, "journal": "Science", "doi": "10.1126/science.aax0364", "pmid": "31672913", "pmcid": "PMC6945816", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Structure; cells", "peer_reviewed": true, "finding": "Structure reveals the FLCN complex as a Rag-GTPase activation checkpoint gating mTORC1.", "url": "https://mtor-atlas.org/study/LAW2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAW2019.json" }, { "sid": "VEL2026", "title": "Anticipatory metabolic regulation drives the distinct and improved metabolic state of caloric restriction compared to Fasting-Refeeding cycles.", "authors": "Velingkaar N; Astafev AA; Prabahar A; Maravillas MA; Trokhimenko E; Rom JB; Asi GJ; Piontkivska H; Jiang P; Kondratov RV", "year": 2026, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2026.118022", "pmid": "42752091", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Comparing caloric restriction (CR, one meal/day) to a fasting-refeeding-fasting (FRF) regimen with matched food intake and fasting duration, CR engages anticipatory, circadian-clock-aligned metabolic control (hepatic mTOR signaling, ketogenesis, metabolic gene coordination), whereas FRF responses track direct nutrient/gastric-emptying cues and disrupt circadian rhythmicity. CR improved glucose and fatty-acid metabolism; FRF caused glucose intolerance and hepatic fat accumulation.", "url": "https://mtor-atlas.org/study/VEL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/VEL2026.json" }, { "sid": "YAN2026B", "title": "Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK", "authors": "Yang Y; et al.; Yang X", "year": 2026, "journal": "Signal Transduction and Targeted Therapy", "doi": "10.1038/s41392-026-02773-7", "pmid": "42736285", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Aged mice (12-month-old) and Hepassocin(Fgl1)-knockout mice, partial-hepatectomy liver regeneration model; correlative human liver tissue (aged vs young)", "peer_reviewed": true, "finding": "Hepassocin (HPS/FGL1), a hepatokine, activates AMPK via an ANXA2-ERK-p90RSK-LKB1 cascade, restraining mTOR activity. Aged HPS-knockout mice show reduced LKB1/AMPK activation and elevated mTOR activity, impaired autophagy, exacerbated cellular senescence, and severely compromised liver regeneration after partial hepatectomy. AMPK agonist AICAR or exogenous HPS rescued the aging/regeneration phenotype.", "url": "https://mtor-atlas.org/study/YAN2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAN2026B.json" }, { "sid": "BAR2012", "title": "Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1", "authors": "Bar-Peled L; Sabatini DM et al.", "year": 2012, "journal": "Cell", "doi": "10.1016/j.cell.2012.07.032", "pmid": "22980980", "pmcid": "PMC3517996", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Ragulator was reported as a guanine-nucleotide exchange factor for RagA/B on the lysosome; later work places Ragulator's exchange activity on RagC and assigns RagA GTP loading to SLC38A9, so the tethering role is the better-established one.", "url": "https://mtor-atlas.org/study/BAR2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAR2012.json" }, { "sid": "SOL2014", "title": "The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice", "authors": "Solon-Biet SM et al.", "year": 2014, "journal": "Cell Metabolism", "doi": "10.1016/j.cmet.2014.02.009", "pmid": "24606899", "pmcid": "PMC5087279", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse, 25 ad libitum diets", "peer_reviewed": true, "finding": "Lifespan and cardiometabolic health were determined not by caloric intake but by the protein:carbohydrate ratio; a low protein ratio was associated with lower hepatic mTOR activation.", "url": "https://mtor-atlas.org/study/SOL2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/SOL2014.json" }, { "sid": "MOT2008", "title": "Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial", "authors": "Motzer RJ et al.", "year": 2008, "journal": "Lancet", "doi": "10.1016/S0140-6736(08)61039-9", "pmid": "18653228", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase III RCT (RECORD-1)", "peer_reviewed": true, "finding": "Everolimus extended median progression-free survival from 1.9 to 4.0 months versus placebo in metastatic renal cell carcinoma.", "url": "https://mtor-atlas.org/study/MOT2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/MOT2008.json" }, { "sid": "JAN2010", "title": "Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor", "authors": "Janes MR; Fruman DA et al.", "year": 2010, "journal": "Nature medicine", "doi": "10.1038/nm.2091", "pmid": "20072130", "pmcid": "PMC4017764", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Leukemia cells; mouse", "peer_reviewed": true, "finding": "The ATP-competitive TORC1/2 inhibitor PP242 selectively kills leukemia cells, with much weaker effects on the proliferation and function of normal lymphocytes.", "url": "https://mtor-atlas.org/study/JAN2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/JAN2010.json" }, { "sid": "BUR1998", "title": "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1", "authors": "Burnett PE; Sabatini DM et al.", "year": 1998, "journal": "Proceedings of the National Academy of Sciences of the United States of America", "doi": "10.1073/pnas.95.4.1432", "pmid": "9465032", "pmcid": "PMC19032", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro", "peer_reviewed": true, "finding": "RAFT1/mTOR directly phosphorylates p70 S6K (Thr389) and 4E-BP1, the two central translational effectors.", "url": "https://mtor-atlas.org/study/BUR1998/", "api_url": "https://mtor-atlas.org/api/v1/studies/BUR1998.json" }, { "sid": "SHW2004", "title": "The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress", "authors": "Shaw RJ; Kosmatka M; Bardeesy N; Cantley LC et al.", "year": 2004, "journal": "Proceedings of the National Academy of Sciences", "doi": "10.1073/pnas.0308061100", "pmid": "14985505", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "LKB1-null MEFs; in vitro kinase assays", "peer_reviewed": true, "finding": "The paper that identified LKB1 as the upstream kinase for AMPK: LKB1 directly phosphorylates AMPK-alpha on Thr172, and LKB1-null cells cannot activate AMPK under energy stress. This is the canonical source for the LKB1 -> AMPK step that gates the whole energy-sensing arm upstream of mTORC1.", "url": "https://mtor-atlas.org/study/SHW2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHW2004.json" }, { "sid": "KUB2012", "title": "Temporal coding of insulin action through multiplexing of the AKT pathway", "authors": "Kubota H; Noguchi R; Toyoshima Y; Ozaki YI; Uda S; Watanabe K; Ogawa W; Kuroda S", "year": 2012, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2012.04.018", "pmid": "22633957", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Rat hepatoma cells (Fao); pulse vs sustained insulin, time-course phosphorylation plus kinetic modelling", "peer_reviewed": true, "finding": "The same pathway can carry different messages in the shape of its signal over time. A short insulin pulse produced transient AKT phosphorylation and a sustained dose produced sustained AKT phosphorylation. S6K read only the transient part, G6Pase only the sustained part and GSK3-beta both. Which output responds depends on the pattern, not just the amount - the clearest cell-level case in the atlas that timing carries information in this pathway.", "url": "https://mtor-atlas.org/study/KUB2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/KUB2012.json" }, { "sid": "SAX2017", "title": "mTOR Signaling in Growth, Metabolism, and Disease", "authors": "Saxton RA; Sabatini DM", "year": 2017, "journal": "Cell", "doi": "10.1016/j.cell.2017.02.004", "pmid": "28283069", "pmcid": "PMC5394987", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review article", "peer_reviewed": true, "finding": "Comprehensive synthesis of mTORC1/mTORC2 signaling, growth regulation, metabolism, and disease relevance.", "url": "https://mtor-atlas.org/study/SAX2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAX2017.json" }, { "sid": "SAB2017", "title": "Twenty-five years of mTOR: Uncovering the link from nutrients to growth", "authors": "Sabatini DM", "year": 2017, "journal": "Proceedings of the National Academy of Sciences of the United States of America", "doi": "10.1073/pnas.1716173114", "pmid": "29078414", "pmcid": "PMC5692607", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Sabatini's 25-year synthesis linking nutrient sensing to growth through mTOR.", "url": "https://mtor-atlas.org/study/SAB2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAB2017.json" }, { "sid": "STR2012", "title": "Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice", "authors": "Strong R; Miller RA; Harrison DE et al.", "year": 2012, "journal": "J Gerontol A Biol Sci Med Sci", "doi": "10.1093/gerona/gls070", "pmid": "22451473", "pmcid": "PMC3598361", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Negative_result", "model_system": "Mouse (genetically heterogeneous, ITP, 3 sites)", "peer_reviewed": true, "finding": "None of five popular longevity compounds had a statistically significant effect on lifespan. The paper explicitly states the ITP's mission is to publish all results, positive or negative - the exact registry model this Atlas should emulate.", "url": "https://mtor-atlas.org/study/STR2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/STR2012.json" }, { "sid": "BRU1999", "title": "Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor", "authors": "Brunet A; Blenis J et al.", "year": 1999, "journal": "Cell", "doi": "10.1016/S0092-8674(00)80595-4", "pmid": "10102273", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cell lines; primary neurons (in vitro)", "peer_reviewed": true, "finding": "Akt phosphorylates the Forkhead transcription factor FKHRL1 (a FOXO family member), driving its cytoplasmic retention via 14-3-3 binding and blocking Fas-ligand-driven apoptosis — the discovery that placed FOXO transcription factors downstream of Akt/PI3K survival signalling.", "url": "https://mtor-atlas.org/study/BRU1999/", "api_url": "https://mtor-atlas.org/api/v1/studies/BRU1999.json" }, { "sid": "DOR2006", "title": "S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth", "authors": "Dorrello NV; Pagano M et al.", "year": 2006, "journal": "Science", "doi": "10.1126/science.1130276", "pmid": "17053147", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "S6K1 triggers betaTRCP-mediated degradation of the tumour suppressor PDCD4 to promote translation.", "url": "https://mtor-atlas.org/study/DOR2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/DOR2006.json" }, { "sid": "HAR2014", "title": "Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males", "authors": "Harrison DE; Miller RA et al.", "year": 2014, "journal": "Aging Cell", "doi": "10.1111/acel.12170", "pmid": "24245565", "pmcid": "PMC3954939", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (genetically heterogeneous, ITP, 3 sites)", "peer_reviewed": true, "finding": "Beyond rapamycin, the same ITP program found acarbose extended male median lifespan by 22% - evidence that the registry surfaces real positive hits too, not only negative results.", "url": "https://mtor-atlas.org/study/HAR2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAR2014.json" }, { "sid": "MAN2018", "title": "TORC1 inhibition enhances immune function and reduces infections in the elderly", "authors": "Mannick JB; Morris M; Hockey HP; Roma G; Beibel M; et al.; Klickstein LB", "year": 2018, "journal": "Science Translational Medicine", "doi": "10.1126/scitranslmed.aaq1564", "pmid": "29997249", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase 2a RCT (n=264, elderly)", "peer_reviewed": true, "finding": "A phase 2a RCT in 264 older adults: 6 weeks of a low-dose combination of BEZ235 (a catalytic PI3K/mTOR inhibitor) and everolimus (RAD001) was associated with fewer reported infections over the following year, plus higher antiviral gene expression and a better flu-vaccine response. The later phase 3 trial of RTB101 (BEZ235) alone (MAN2021) did not confirm a clinical benefit.", "url": "https://mtor-atlas.org/study/MAN2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAN2018.json" }, { "sid": "ZHANG2026", "title": "Non-canonical mTORC1-TFEB activation promotes hepatocyte plasticity and high-grade malignancy in hepatocellular carcinoma.", "authors": "Zhang C; Chao X; Williams SN; Wei X; DiGirolamo A; et al.", "year": 2026, "journal": "The Journal of clinical investigation", "doi": "10.1172/JCI206334", "pmid": "42560776", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse + Human (HCC)", "peer_reviewed": true, "finding": "TSC1 loss drives non-canonical mTORC1-mediated TFEB nuclear translocation, promoting hepatocyte-to-biliary plasticity and spontaneous aggressive HCC in mice; Tsc1/Tfeb double knockout rescues the phenotype.", "url": "https://mtor-atlas.org/study/ZHANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHANG2026.json" }, { "sid": "CAO2026B", "title": "Dihydromyricetin attenuates fibrosis-associated features of hypertrophic scar with accompanying changes in PI3K/AKT/mTOR-related signaling.", "authors": "Cao P; Shi A; Wang Y; Hui S; Lyu G", "year": 2026, "journal": "Frontiers in Pharmacology", "doi": "10.3389/fphar.2026.1862651", "pmid": "42656474", "pmcid": "PMC13506778", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rabbit ear hypertrophic scar model; human hypertrophic scar fibroblasts", "peer_reviewed": true, "finding": "Dihydromyricetin reduced collagen I/III and α-SMA in hypertrophic scar fibroblasts and improved scar elevation in a rabbit ear model, with accompanying reductions in AKT and mTOR phosphorylation; causality was not established.", "url": "https://mtor-atlas.org/study/CAO2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAO2026B.json" }, { "sid": "SANG2026", "title": "\"Trojan\" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway", "authors": "Sang Z; Zheng Y; Wang X; Wu C; Zhao J; Wang JJ; Sui S; Wang J", "year": 2026, "journal": "Journal of the American Chemical Society", "doi": "10.1021/jacs.6c06772", "pmid": "42677553", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (chemoproteomics / photoaffinity probe)", "peer_reviewed": true, "finding": "Identifies PKM2 as a direct methionine sensor for mTORC1. A photoaffinity methionine analogue plus chemoproteomics showed that PKM2 binds free methionine through a distinct recognition pocket — independently of its glycolytic enzyme activity — and transduces methionine availability to mTORC1 via the GATOR2 complex. Complements SAMTOR (GU2017), which reads the methionine metabolite SAM rather than methionine itself, and suggests a route to a pharmacological \"methionine pseudostarvation\" state.", "url": "https://mtor-atlas.org/study/SANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SANG2026.json" }, { "sid": "LIU2020", "title": "mTOR at the nexus of nutrition, growth, ageing and disease", "authors": "Liu GY; Sabatini DM", "year": 2020, "journal": "Nature Reviews Molecular Cell Biology", "doi": "10.1038/s41580-019-0199-y", "pmid": "31937935", "pmcid": "PMC7102936", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (comprehensive)", "peer_reviewed": true, "finding": "The flagship modern review of the whole field, from Sabatini's own lab (Nature Reviews Molecular Cell Biology). Maps 25+ years of mTOR biology - how it senses nutrients, controls growth and autophagy, and goes wrong in cancer, neurodegeneration, metabolic disease and aging. The single best orientation document for the entire Atlas.", "url": "https://mtor-atlas.org/study/LIU2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIU2020.json" }, { "sid": "BANERJEE2026", "title": "Decoding the PI3K/Akt/mTOR-JAK/STAT signaling axis in multiple sclerosis: mechanistic crosstalk and therapeutic opportunities.", "authors": "Banerjee C; Singh RK; Choudhary D; Khan MN; Maurya PK; Khan Z et al.", "year": 2026, "journal": "Immunologic research", "doi": "10.1007/s12026-026-09808-9", "pmid": "42467315", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review mapping the mechanistic crosstalk between PI3K/Akt/mTOR and JAK/STAT pathways in MS neuroinflammation, identifying dual-pathway mTOR targeting as a therapeutic opportunity to reduce immune dysregulation and demyelination.", "url": "https://mtor-atlas.org/study/BANERJEE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/BANERJEE2026.json" }, { "sid": "SAR2004", "title": "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton", "authors": "Sarbassov DD; Ali SM; Kim DH; Guertin DA; Latek RR; Erdjument-Bromage H; Tempst P; Sabatini DM", "year": 2004, "journal": "Current Biology", "doi": "10.1016/j.cub.2004.06.054", "pmid": "15268862", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + Drosophila", "peer_reviewed": true, "finding": "Discovery of Rictor and the SECOND mTOR complex, mTORC2. Crucially showed this complex is NOT blocked by rapamycin and does not use Raptor - it controls the cytoskeleton via PKC. This is the paper that split mTOR biology into 'two faces' at the molecular level.", "url": "https://mtor-atlas.org/study/SAR2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAR2004.json" }, { "sid": "LAB2015", "title": "mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation", "authors": "Laberge RM; Sun Y; Orjalo AV; Patil CK; Freund A; et al.; Campisi J", "year": 2015, "journal": "Nature Cell Biology", "doi": "10.1038/ncb3195", "pmid": "26147250", "pmcid": "PMC4691706", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + mouse xenografts", "peer_reviewed": true, "finding": "Explained HOW rapamycin calms 'inflammaging'. Senescent cells spew inflammatory signals (the SASP) that damage surrounding tissue and even feed tumors. mTOR powers this by translating IL1A, the cytokine at the top of the cascade. Rapamycin selectively shuts it down - and blocked senescent cells from fueling prostate tumor growth in mice.", "url": "https://mtor-atlas.org/study/LAB2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAB2015.json" }, { "sid": "KIN2026", "title": "TCR-mTORC1 signaling promotes epigenetic stabilization of Foxp3 expression in regulatory T cells via TET protein translation", "authors": "Kinoshita T; Hori S et al.", "year": 2026, "journal": "Proceedings of the National Academy of Sciences of the United States of America", "doi": "10.1073/pnas.2612904123", "pmid": "42809396", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse; in vitro-induced regulatory T cells (iTreg)", "peer_reviewed": true, "finding": "Sustained TCR signaling activates mTORC1, which boosts translation of the TET2 (and likely TET3) DNA-demethylation enzymes; this demethylates the Foxp3 TSDR enhancer and epigenetically locks in stable Foxp3 expression in regulatory T cells. In vivo mTORC1 inactivation increases methylated-TSDR Foxp3+ T cells, confirming the pathway's physiological relevance.", "url": "https://mtor-atlas.org/study/KIN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIN2026.json" }, { "sid": "MAR2012", "title": "MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB", "authors": "Martina JA; Chen Yong; Gucek M; Puertollano R", "year": 2012, "journal": "Autophagy", "doi": "10.4161/auto.19653", "pmid": "22576015", "pmcid": "PMC3427256", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells", "peer_reviewed": true, "finding": "Showed mTORC1-dependent TFEB Ser211 phosphorylation: mTORC1 (docked at the lysosome via Ragulator) phosphorylates TFEB on Ser211, which traps it in the cytosol via 14-3-3 proteins. Inhibit mTORC1 and TFEB rushes to the nucleus to switch on autophagy - explaining how mTORC1 controls recycling at the level of gene transcription.", "url": "https://mtor-atlas.org/study/MAR2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAR2012.json" }, { "sid": "KNO2026", "title": "The hallmarks of protein and amino acid restriction in aging and longevity", "authors": "Knopf BA; Lamming DW", "year": 2026, "journal": "Cell Press Blue", "doi": "10.1016/j.cpblue.2026.100079", "pmid": "42639474", "pmcid": "PMC13501984", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Cross-species review (yeast, worm, fly, rodent, human)", "peer_reviewed": true, "finding": "Defines the \"hallmarks\" of dietary protein restriction (PR) through the lens of aging: PR and restriction of specific essential amino acids — especially methionine, isoleucine and valine — improve metabolic health, healthspan and lifespan across organisms, with amino-acid composition (not just protein quantity) acting as a key determinant via nutrient-sensing pathways including mTORC1.", "url": "https://mtor-atlas.org/study/KNO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/KNO2026.json" }, { "sid": "PAR2014", "title": "Sestrins inhibit mTORC1 kinase activation through the GATOR complex", "authors": "Parmigiani A; Budanov AV et al.", "year": 2014, "journal": "Cell reports", "doi": "10.1016/j.celrep.2014.10.019", "pmid": "25457612", "pmcid": "PMC4303546", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Sestrins inhibit mTORC1 activation through the GATOR2 complex.", "url": "https://mtor-atlas.org/study/PAR2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/PAR2014.json" }, { "sid": "KIM2019", "title": "mTOR as a central hub of nutrient signalling and cell growth", "authors": "Kim J; Guan KL et al.", "year": 2019, "journal": "Nature cell biology", "doi": "10.1038/s41556-018-0205-1", "pmid": "30602761", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review: mTOR as a central hub of nutrient signalling and cell growth.", "url": "https://mtor-atlas.org/study/KIM2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2019.json" }, { "sid": "LV2026", "title": "Age-associated decline of Lamtor5 drives immunosenescence and systemic aging via cGAS-mediated paracrine inflammation.", "authors": "Lv N, Tang Y, Zhang W, Zhang S, Zhang M", "year": 2026, "journal": "Cell Death and Differentiation", "doi": "10.1038/s41418-026-01823-5", "pmid": "42463581", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Age-driven loss of Lamtor5, a key lysosomal mTOR activation complex subunit, drives macrophage immunosenescence and systemic aging phenotypes in mice by unleashing cGAS-STING paracrine inflammation; restoring Lamtor5 in aged mice rescued immunosenescence and attenuated systemic ageing phenotypes.", "url": "https://mtor-atlas.org/study/LV2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LV2026.json" }, { "sid": "VAL2019", "title": "Molecular logic of mTORC1 signalling as a metabolic rheostat", "authors": "Valvezan AJ; Manning BD et al.", "year": 2019, "journal": "Nature metabolism", "doi": "10.1038/s42255-019-0038-7", "pmid": "32694720", "pmcid": "PMC12569966", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review framing mTORC1 as a metabolic rheostat coupling growth signals to metabolism.", "url": "https://mtor-atlas.org/study/VAL2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/VAL2019.json" }, { "sid": "HON2026", "title": "Structure and function of TM6SF1 reveals role in mTORC1 signaling", "authors": "Hong S; Li X et al.", "year": 2026, "journal": "Proceedings of the National Academy of Sciences", "doi": "10.1073/pnas.2622424123", "pmid": "42735304", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure; HEK293 cells", "peer_reviewed": true, "finding": "Cryo-EM structure of TM6SF1 identifies it as a lysosomal cholesterol-binding protein that directly engages LAMTOR1 (Ragulator) to regulate mTORC1 signaling in a cholesterol-dependent manner.", "url": "https://mtor-atlas.org/study/HON2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HON2026.json" }, { "sid": "HU2026", "title": "Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy", "authors": "Hu Y; Li W; Hu M; Tian S; Zhou S; Liu J; Cheng X; Zhang C; Zuo Y; Zhang J; Liu D; Hu Y; Chen Y; Li X; Luo L; Yang H; Bai L; Liu H; Ferdinandy P; Chiong M; Troncoso MF; Wen J; Cai J; Zhang XJ; She ZG; Zhang X; Li H", "year": 2026, "journal": "Circulation", "doi": "10.1161/CIRCULATIONAHA.126.080371", "pmid": "42770220", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat cardiomyocytes (adenoviral overexpression/knockdown); mouse cardiomyocyte-specific AAV9 overexpression and knockout, transverse aortic constriction (TAC) model", "peer_reviewed": true, "finding": "Identifies LAPTM4A, a lysosomal transmembrane protein, as a novel booster of mTORC1 signaling in cardiomyocytes: LAPTM4A binds NEDD4L, driving K63-linked ubiquitination of AKT and downstream mTORC1-p70S6K/4EBP1-mediated protein synthesis, without affecting lysosomal autophagy. Cardiomyocyte-specific LAPTM4A deletion attenuated TAC-induced hypertrophy/fibrosis in mice; an FDA-approved-drug screen identified magnolol as a LAPTM4A suppressor with cardioprotective effect in vivo.", "url": "https://mtor-atlas.org/study/HU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HU2026.json" }, { "sid": "FRI2006", "title": "mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s", "authors": "Frias MA; Sabatini DM et al.", "year": 2006, "journal": "Current biology : CB", "doi": "10.1016/j.cub.2006.08.001", "pmid": "16919458", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mSin1 is required for mTORC2 assembly and Akt Ser473 phosphorylation; isoforms define distinct complexes.", "url": "https://mtor-atlas.org/study/FRI2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/FRI2006.json" }, { "sid": "YAN2006", "title": "Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity", "authors": "Yang Q; Guan KL et al.", "year": 2006, "journal": "Genes & development", "doi": "10.1101/gad.1461206", "pmid": "17043309", "pmcid": "PMC1619946", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Identified Sin1 as an essential TORC2 component required for Akt phosphorylation.", "url": "https://mtor-atlas.org/study/YAN2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAN2006.json" }, { "sid": "GUE2007", "title": "Defining the role of mTOR in cancer", "authors": "Guertin DA; Sabatini DM", "year": 2007, "journal": "Cancer Cell", "doi": "10.1016/j.ccr.2007.05.008", "pmid": "17613433", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review article", "peer_reviewed": true, "finding": "Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology.", "url": "https://mtor-atlas.org/study/GUE2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUE2007.json" }, { "sid": "LI2026C", "title": "mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis", "authors": "Li TL; Blair JD; Yoo T; Grant GA; Hockemeyer D; Porter BE; Bateup HS", "year": 2026, "journal": "Nature", "doi": "10.1038/s41586-026-11054-w", "pmid": "42778607", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human iPSC-derived brain organoids (TSC2-mutant); resected cortical tuber tissue from TSC patients", "peer_reviewed": true, "finding": "Using human brain organoids carrying TSC2 loss-of-function mutations plus patient-derived cortical tuber tissue, shows that hyperactive mTORC1 signaling drives neural progenitors to differentiate into enlarged, pro-inflammatory reactive astrocytes in a cell-autonomous manner (downregulated glutamate transporters, elevated inflammatory cytokines and AD-risk genes APOE/CLU) — independent of seizure activity. Positions glial dysfunction as a primary driver of TSC pathology, not merely a downstream consequence.", "url": "https://mtor-atlas.org/study/LI2026C/", "api_url": "https://mtor-atlas.org/api/v1/studies/LI2026C.json" }, { "sid": "BEN2013", "title": "Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1", "authors": "Ben-Sahra I; Manning BD et al.", "year": 2013, "journal": "Science", "doi": "10.1126/science.1228792", "pmid": "23429703", "pmcid": "PMC3753690", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1-S6K1 stimulates de novo pyrimidine synthesis by phosphorylating CAD.", "url": "https://mtor-atlas.org/study/BEN2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/BEN2013.json" }, { "sid": "KHA2014", "title": "BMAL1-dependent regulation of the mTOR signaling pathway delays aging", "authors": "Khapre RV; Kondratova AA; Patel S; Dubrovsky Y; Wrobel M; Antoch MP; Kondratov RV", "year": 2014, "journal": "Aging (Albany NY)", "doi": "10.18632/aging.100633", "pmid": "24481314", "pmcid": "PMC3927809", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Bmal1-/- mice and fibroblasts", "peer_reviewed": true, "finding": "Loss of the clock protein BMAL1 raised mTORC1 activity in mice and in cultured cells, and rapamycin extended the lifespan of Bmal1-/- mice by 50%. Places the circadian clock upstream of mTORC1 as a brake, and links that brake to ageing.", "url": "https://mtor-atlas.org/study/KHA2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/KHA2014.json" }, { "sid": "BAT2022", "title": "mTOR substrate phosphorylation in growth control", "authors": "Battaglioni S; Hall MN et al.", "year": 2022, "journal": "Cell", "doi": "10.1016/j.cell.2022.04.013", "pmid": "35580586", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review cataloguing direct mTOR substrates and how mTORC1/2 achieve substrate specificity.", "url": "https://mtor-atlas.org/study/BAT2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAT2022.json" }, { "sid": "BJE2010", "title": "Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster", "authors": "Bjedov I; Partridge L et al.", "year": 2010, "journal": "Cell Metabolism", "doi": "10.1016/j.cmet.2009.11.010", "pmid": "20074526", "pmcid": "PMC2824086", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila melanogaster", "peer_reviewed": true, "finding": "Feeding rapamycin extended fly lifespan through autophagy and reduced translation, and worked even in flies already on a lifespan-maximizing diet.", "url": "https://mtor-atlas.org/study/BJE2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/BJE2010.json" }, { "sid": "NAP2020", "title": "A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dube syndrome", "authors": "Napolitano G; Ballabio A et al.", "year": 2020, "journal": "Nature", "doi": "10.1038/s41586-020-2444-0", "pmid": "32612235", "pmcid": "PMC7610377", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells; mouse", "peer_reviewed": true, "finding": "A substrate-specific mTORC1-TFEB pathway (RagC/D-dependent) drives Birt-Hogg-Dube kidney disease.", "url": "https://mtor-atlas.org/study/NAP2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/NAP2020.json" }, { "sid": "CHEN2026B", "title": "IGF2BP3-Mediated m6A Modification of OLR1 mRNA Promotes Immune Evasion in CRC via the PI3K/AKT/mTOR Pathway", "authors": "Chen W", "year": 2026, "journal": "Journal of Immunotherapy", "doi": "10.1097/CJI.0000000000000613", "pmid": null, "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "CRC cell lines (human); TCGA dataset", "peer_reviewed": true, "finding": "IGF2BP3 stabilizes OLR1 via m6A RNA modification, activating PI3K/AKT/mTOR signaling which suppresses CD8+ T cell anti-tumor activity and drives immune evasion in colorectal cancer.", "url": "https://mtor-atlas.org/study/CHEN2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHEN2026B.json" }, { "sid": "CUI2025", "title": "Structural basis for mTORC1 activation on the lysosomal membrane", "authors": "Cui Z; Esposito A; Napolitano G; Ballabio A; Hurley JH", "year": 2025, "journal": "Nature", "doi": "10.1038/s41586-025-09545-3", "pmid": "40963021", "pmcid": "PMC12448111", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure (human proteins, reconstituted on membranes)", "peer_reviewed": true, "finding": "Resolves how mTORC1 flips from 'parked on the lysosome' to 'catalytically switched on'. Reconstituting the whole assembly on membranes from purified Rheb, Rag GTPases, Ragulator and mTORC1, cryo-EM shows the kinase reaches full activity only after two separate anchoring steps: Rag-Ragulator first pulls it to within about 100 angstroms of the membrane, then Rheb pulls it to within about 40 angstroms, and only when Raptor and mTOR itself also touch the membrane directly do the catalytic residues line up for full activity. Growth-factor input (via Rheb) and nutrient input (via the Rags) are shown converging on the same physical docking event rather than acting through separate switches. Boundary: reconstituted on synthetic membranes from purified components — a structural/biochemical model, not a measurement inside a living cell.", "url": "https://mtor-atlas.org/study/CUI2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/CUI2025.json" }, { "sid": "CAC2010", "title": "Molecular interplay between mTOR, amyloid-beta, and Tau: effects on cognitive impairments", "authors": "Caccamo A; Majumder S; Richardson A; Strong R; Oddo S", "year": 2010, "journal": "Journal of Biological Chemistry", "doi": "10.1074/jbc.M110.100420", "pmid": "20178983", "pmcid": "PMC2857107", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "3xTg-AD transgenic mice", "peer_reviewed": true, "finding": "Revealed a vicious cycle: amyloid-beta RAISES mTOR activity, and high mTOR in turn blocks the autophagy needed to clear amyloid and tau - so the disease feeds itself. Rapamycin broke the loop in 3xTg-AD mice, rescuing memory and lowering BOTH amyloid and tau, with autophagy induction shown to be necessary for the reduction in amyloid levels.", "url": "https://mtor-atlas.org/study/CAC2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAC2010.json" }, { "sid": "BIS2013", "title": "Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial", "authors": "Bissler JJ; Kingswood JC; Radzikowska E; Zonnenberg BA; Frost M; et al.; Budde K", "year": 2013, "journal": "Lancet", "doi": "10.1016/S0140-6736(12)61767-X", "pmid": "23312829", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase 3 RCT (n=118, TSC/LAM)", "peer_reviewed": true, "finding": "The companion phase 3 RCT (n=118) to EXIST-1, targeting kidney tumors (angiomyolipomas) in tuberous sclerosis and LAM. Everolimus shrank them by >=50% in 42% of patients versus 0% on placebo. Together EXIST-1 and -2 sealed everolimus as a disease-modifying therapy across multiple TSC tumor types.", "url": "https://mtor-atlas.org/study/BIS2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/BIS2013.json" }, { "sid": "GUE2020", "title": "Crosstalk dynamics between the circadian clock and the mTORC1 pathway", "authors": "Guerrero-Morín JG; Santillán M", "year": 2020, "journal": "Journal of Theoretical Biology", "doi": "10.1016/j.jtbi.2020.110360", "pmid": "32522472", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Deterministic differential-algebraic equation model (in silico only)", "peer_reviewed": true, "finding": "A mathematical model of how mTORC1 could tune the circadian clock. It suggests mTORC1 raises clock amplitude by controlling BMAL1 translation and shortens the period by controlling where BMAL1 sits in the cell, and that both levels are needed for robust oscillation. A model, not a measurement - it proposes mechanisms for RAM2018's observations rather than testing them.", "url": "https://mtor-atlas.org/study/GUE2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUE2020.json" }, { "sid": "DEMMINGS2026", "title": "ATF4 activates a transcriptional program that chronically suppresses mTOR activity and promotes neurodegeneration in Parkinson disease models", "authors": "Demmings MD; Kane EA; Tennyson EC; Hurley K; Zhao J; Cruickshanks NA; Ciz V; Krupa JM; Pasternak SH; Cregan SP", "year": 2026, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2026.117832", "pmid": "42599806", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse (neurotoxin and alpha-synucleinopathy PD models) and cultured neurons", "peer_reviewed": true, "finding": "Chronic integrated-stress-response signalling through ATF4 coordinately upregulates SESN2, DDIT4 and Trib3, which together suppress BOTH mTORC1 and mTORC2; this sustained mTOR inhibition drives dopaminergic neuron death via the pro-apoptotic BCL-2 family protein PUMA. Defines a maladaptive ISR/ATF4-to-mTOR axis in Parkinson disease models — a case where LESS mTOR activity is harmful, opposite to the usual longevity framing.", "url": "https://mtor-atlas.org/study/DEMMINGS2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEMMINGS2026.json" }, { "sid": "MOS2018", "title": "mTOR signalling and cellular metabolism are mutual determinants in cancer", "authors": "Mossmann D; Hall MN et al.", "year": 2018, "journal": "Nature reviews. Cancer", "doi": "10.1038/s41568-018-0074-8", "pmid": "30425336", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of mTOR and cellular metabolism as mutual determinants in cancer.", "url": "https://mtor-atlas.org/study/MOS2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/MOS2018.json" }, { "sid": "BETZ2013", "title": "Where is mTOR and what is it doing there?", "authors": "Betz C; Hall MN et al.", "year": 2013, "journal": "The Journal of cell biology", "doi": "10.1083/jcb.201306041", "pmid": "24385483", "pmcid": "PMC3840941", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of where mTOR localizes and its compartmentalized functions.", "url": "https://mtor-atlas.org/study/BETZ2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/BETZ2013.json" }, { "sid": "EIS2016", "title": "Cardioprotection and lifespan extension by the natural polyamine spermidine", "authors": "Eisenberg T; Abdellatif M; Schroeder S; Primessnig U; Stekovic S; Pendl T; Harger A; Schipke J; Zimmermann A; Schmidt A; Tong M; Ruckenstuhl C; Dammbrueck C; Gross AS; Herbst V; Magnes C; Trausinger G; Narath S; Meinitzer A; Hu Z; Kirsch A; Eller K; Carmona-Gutierrez D; Buettner S; Pietrocola F; Knittelfelder O; Schrepfer E; Rockenfeller P; Simonini C; Rahn A; Horsch M; Moreth K; Beckers J; Fuchs H; Gailus-Durner V; Neff F; Janik D; Rathkolb B; Rozman J; de Angelis MH; Moustafa T; Haemmerle G; Mayr M; Willeit P; von Frieling-Salewsky M; Pieske B; Scorrano L; Pieber T; Pechlaner R; Willeit J; Sigrist SJ; Linke WA; Muehlfeld C; Sadoshima J; Dengjel J; Kiechl S; Sedej S; Madeo F", "year": 2016, "journal": "Nat Med", "doi": "10.1038/nm.4222", "pmid": "27841876", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mice, Dahl salt-sensitive rats, plus a human dietary cohort", "peer_reviewed": true, "finding": "The mammalian follow-up to EIS2009 and the reason the spermidine branch matters for human health claims: oral spermidine extends mouse lifespan, reduces cardiac hypertrophy and preserves diastolic function, and the protection disappears in mice whose cardiomyocytes lack Atg5, which makes autophagy necessary rather than merely correlated. Boundary: the human part is a dietary questionnaire correlated with blood pressure and cardiovascular incidence, so it is observational and does not carry the causal claim the mouse data carry.", "url": "https://mtor-atlas.org/study/EIS2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/EIS2016.json" }, { "sid": "BYF2005", "title": "hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase", "authors": "Byfield MP; Murray JT; Backer JM", "year": 2005, "journal": "J Biol Chem", "doi": "10.1074/jbc.M507201200", "pmid": "16049009", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human and hamster cell lines (HeLa, CHO)", "peer_reviewed": true, "finding": "Opens a second, non-canonical route by which amino acids reach mTORC1. The class III PI 3-kinase hVps34 is switched off by amino acid or glucose starvation and by AMPK activation, and is required for S6K1 and 4E-BP1 phosphorylation, yet it sits outside the insulin/class I PI3K input (it does not affect Akt or TSC2 phosphorylation). Boundary: cell lines and knockdown/overexpression only; the step is nutrient-regulated but the sensor itself is not identified.", "url": "https://mtor-atlas.org/study/BYF2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/BYF2005.json" }, { "sid": "SU2026", "title": "LncRNA DLX6-AS1 promotes necroptosis through PI3K/AKT/mTOR signaling pathway in myocardial ischemia/reperfusion injury mice", "authors": "Su Y; Mu L; Wang L; Li T; Zhang Q; Zhang Jun", "year": 2026, "journal": "Scientific Reports", "doi": "10.1038/s41598-026-50371-y", "pmid": "42601357", "pmcid": "PMC13476243", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse; Rat H9c2 cells", "peer_reviewed": true, "finding": "LncRNA DLX6-AS1 activates PI3K/AKT/mTOR signaling to promote necroptosis in myocardial ischemia-reperfusion injury; inhibiting DLX6-AS1 suppresses necroptosis and protects cardiomyocytes.", "url": "https://mtor-atlas.org/study/SU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SU2026.json" }, { "sid": "HARA2002", "title": "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action", "authors": "Hara K; Maruki Y; Long X; Yoshino K; Oshiro N; Hidayat S; Tokunaga C; Avruch J; Yonezawa K", "year": 2002, "journal": "Cell", "doi": "10.1016/s0092-8674(02)00833-4", "pmid": "12150926", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + C. elegans RNAi", "peer_reviewed": true, "finding": "Independent co-discovery of Raptor (same issue of Cell as Kim 2002). Showed Raptor is essential for mTOR to phosphorylate 4E-BP1 and S6K1, and that knocking it down in worms mimics loss of TOR - confirming Raptor as a core, conserved mediator of TOR action.", "url": "https://mtor-atlas.org/study/HARA2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/HARA2002.json" }, { "sid": "ZEN2013", "title": "mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function", "authors": "Zeng H; Chi H et al.", "year": 2013, "journal": "Nature", "doi": "10.1038/nature12297", "pmid": "23812589", "pmcid": "PMC3759242", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "mTORC1 couples immune signals and metabolism to establish regulatory T-cell function.", "url": "https://mtor-atlas.org/study/ZEN2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZEN2013.json" }, { "sid": "ROD2011", "title": "mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling", "authors": "Rodrik-Outmezguine VS; Rosen N et al.", "year": 2011, "journal": "Cancer discovery", "doi": "10.1158/2159-8290.CD-11-0085", "pmid": "22140653", "pmcid": "PMC3227125", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells", "peer_reviewed": true, "finding": "mTOR kinase inhibition triggers feedback-dependent biphasic AKT reactivation, informing resistance.", "url": "https://mtor-atlas.org/study/ROD2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROD2011.json" }, { "sid": "NAT2026", "title": "mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment", "authors": "Nath P; Khandelwal A; Li C; Moore-Medlin T; Vasudevan SS; Alvarez VA; Franco OE; Gutkind JS; Nathan CO", "year": 2026, "journal": "Neoplasia", "doi": "10.1016/j.neo.2026.101350", "pmid": "42570420", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Syngeneic mouse models of TP53-mutant HNSCC", "peer_reviewed": true, "finding": "In syngeneic TP53-mutant HNSCC mouse models, the mTOR inhibitor everolimus reprogrammed the immune-cold tumor microenvironment: it increased CD8+ T cell and dendritic cell infiltration, reduced Tregs and HIF-1α/VEGFA-driven MDSC recruitment, boosted TNF-α/CXCL10 chemokine signaling, and reduced PD-1/PD-L1 expression — restoring T-cell cytotoxic competence and suppressing tumor growth.", "url": "https://mtor-atlas.org/study/NAT2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/NAT2026.json" }, { "sid": "NAR2011", "title": "Spatial coupling of mTOR and autophagy augments secretory phenotypes", "authors": "Narita Masako; Young AR; Arakawa S; Samarajiwa SA; Nakashima T; Yoshida S; Hong S; Berry LS; Reichelt S; Ferreira M; Tavare S; Inoki K; Shimizu S; Narita Masashi", "year": 2011, "journal": "Science", "doi": "10.1126/science.1205407", "pmid": "21512002", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human and mouse cells (Ras-induced senescent fibroblasts, macrophages, podocytes)", "peer_reviewed": true, "finding": "Protein synthesis and autophagic degradation are usually described as opposites that mTOR switches between, and this paper shows a compartment where the cell deliberately runs both at once. In senescent cells, autolysosomes and mTOR gather at one side of the Golgi (the TASCC), mTOR gets there in an amino-acid- and Rag-dependent way, and destroying that arrangement cuts interleukin-6/8 secretion. Boundary: cells, not organisms; it explains how the senescent secretory programme is fuelled, not whether blocking it helps an animal.", "url": "https://mtor-atlas.org/study/NAR2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/NAR2011.json" }, { "sid": "VAL2017", "title": "mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability", "authors": "Valvezan AJ; Manning BD et al.", "year": 2017, "journal": "Cancer cell", "doi": "10.1016/j.ccell.2017.09.013", "pmid": "29056426", "pmcid": "PMC5687294", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells; tumor", "peer_reviewed": true, "finding": "Hyperactive mTORC1 couples nucleotide synthesis to demand; imbalance drives replication stress in these cells.", "url": "https://mtor-atlas.org/study/VAL2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/VAL2017.json" }, { "sid": "PRE2021", "title": "G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling", "authors": "Prentzell MT; Rehbein U; Cadena Sandoval M; De Meulemeester AS; Baumeister R; et al.; Carroll B; Demetriades C; Korolchuk VI; Nellist M; Palm W; Sampson JR; Teleman AA; Opitz CA; Thedieck K", "year": 2021, "journal": "Cell", "doi": "10.1016/j.cell.2020.12.024", "pmid": "33497611", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human and mouse cells; breast cancer patient data; zebrafish", "peer_reviewed": true, "finding": "Adds a physical brake upstream of mTORC1. G3BP1 and G3BP2, known until then as core stress-granule proteins, also sit on the cytoplasmic face of the lysosome and are what holds the TSC complex there; without them TSC cannot reach its target and mTORC1 becomes over-responsive to amino acids and insulin. Loss of G3BP1 reproduces TSC-like hyperactivity phenotypes: faster mTORC1-driven motility in breast cancer cells, with low G3BP1 correlating with worse patient outcome, and disturbed neuronal development in zebrafish. Relevant to the Atlas because it is a lysosomal tethering step that the canonical Rheb/TSC diagram does not show.", "url": "https://mtor-atlas.org/study/PRE2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/PRE2021.json" }, { "sid": "HAN2008", "title": "A role for autophagy in the extension of lifespan by dietary restriction in C. elegans", "authors": "Hansen M; Chandra A; Mitic LL; Onken B; Driscoll M; Kenyon C", "year": 2008, "journal": "PLoS Genet", "doi": "10.1371/journal.pgen.0040024", "pmid": "18282106", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Caenorhabditis elegans", "peer_reviewed": true, "finding": "Makes autophagy a necessary step between dietary restriction and a longer life, not a side effect of it: blocking autophagy genes abolishes the lifespan extension produced both by dietary restriction and by TOR inhibition. The paper is equally careful about what autophagy cannot do on its own, because autophagy still runs in animals lacking DAF-16/FOXO and yet those animals are not long-lived. Boundary: worms; necessity was shown, sufficiency was not.", "url": "https://mtor-atlas.org/study/HAN2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAN2008.json" }, { "sid": "XU2026", "title": "High Responsiveness of Head and Neck Kaposiform Hemangioendothelioma Without Kasabach-Merritt Phenomenon to Sirolimus Monotherapy.", "authors": "Xu Y; Zhou J; Lan Y et al.", "year": 2026, "journal": "Pediatric Blood & Cancer", "doi": "10.1002/1545-5017.70635", "pmid": "42657977", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (paediatric multicentre matched cohort, n=71)", "peer_reviewed": true, "finding": "In 71 children with kaposiform haemangioendothelioma without Kasabach-Merritt phenomenon, head and neck lesions achieved a 100% 12-month radiologic response to sirolimus monotherapy versus 76% elsewhere; anatomical location was the only independent predictor of response. Observational: a matched multicentre cohort, not a randomised comparison, so confounding by indication and by lesion characteristics cannot be excluded and the association between site and response is not established as causal.", "url": "https://mtor-atlas.org/study/XU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/XU2026.json" }, { "sid": "KRISTIANSEN2026", "title": "Aging preserves mTORC1 but attenuates JNK-SMAD2L signaling sensitivity to passive stretch-induced tension development in isolated mouse skeletal muscle.", "authors": "Kristiansen JB; Andresen J; Jakobsgaard JE; Vissing K", "year": 2026, "journal": "Experimental gerontology", "doi": "10.1016/j.exger.2026.113265", "pmid": "42551770", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (ex vivo EDL muscle, adult 16-week vs old 24-month female mice)", "peer_reviewed": true, "finding": "Passive mechanical stretch activated mTORC1 signalling (mTOR, p70S6K, rpS6, 4E-BP1) to a similar degree in ex vivo muscle from adult and old female mice, whereas JNK-SMAD2L activation by the same stretch was blunted with age, suggesting mTORC1 mechanosensitivity itself is preserved in this model.", "url": "https://mtor-atlas.org/study/KRISTIANSEN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/KRISTIANSEN2026.json" }, { "sid": "KEN2016", "title": "The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging", "authors": "Kennedy BK; Lamming DW", "year": 2016, "journal": "Cell Metabolism", "doi": "10.1016/j.cmet.2016.05.009", "pmid": "27304501", "pmcid": "PMC4910876", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (metabolism/aging)", "peer_reviewed": true, "finding": "A Cell Metabolism review framing mTOR as the 'grand conductor' that coordinates whole-body metabolism, tissue by tissue. Especially valuable for its clear-eyed section on WHY rapamycin causes metabolic side effects (the mTORC2 problem) - which is the main barrier to using it against aging. Pairs perfectly with Lamming's own 2012 mechanism paper.", "url": "https://mtor-atlas.org/study/KEN2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/KEN2016.json" }, { "sid": "HAL2012", "title": "Chronic inhibition of mTOR by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice", "authors": "Halloran J; Hussong SA; Burbank R; Podlutskaya N; Fischer KE; et al.; Galvan V", "year": 2012, "journal": "Neuroscience", "doi": "10.1016/j.neuroscience.2012.06.054", "pmid": "22750207", "pmcid": "PMC3454865", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "C57BL/6 mice (lifespan behavior study)", "peer_reviewed": true, "finding": "Asked whether the lifespan-extending dose of rapamycin harms or helps the aging BRAIN. Reassuringly, it enhanced learning and memory in young mice, prevented age-related cognitive decline in old ones, and even reduced anxiety and depression-like behavior - linked to boosted brain monoamines. Cognitive benefit, not cost.", "url": "https://mtor-atlas.org/study/HAL2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAL2012.json" }, { "sid": "LAP2012", "title": "mTOR signaling in growth control and disease", "authors": "Laplante M; Sabatini DM", "year": 2012, "journal": "Cell", "doi": "10.1016/j.cell.2012.03.017", "pmid": "22500797", "pmcid": "PMC3331679", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (comprehensive)", "peer_reviewed": true, "finding": "The classic 2012 Cell review that became the standard reference for mTOR signaling. Comprehensive yet readable synthesis of how mTOR integrates environmental cues to control growth, and how its deregulation drives cancer, obesity, diabetes and neurodegeneration. A perfect companion to the newer 2020 review.", "url": "https://mtor-atlas.org/study/LAP2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAP2012.json" }, { "sid": "ZAU2026", "title": "mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation", "authors": "Zaufel A; Sun W; Pastore N; Taschler U; Wagner C; Hackl H; Sommer J; Silbert-Wagner D; Hengstler JG; Begher-Tibbe B; Stauber R; Kolb D; Troetzmueller M; Gottschalk B; Thorsheim C; Stange EL; Hornef MW; Pivovarova-Ramich O; Pfeiffer AFH; Matchett KP; Loft A; Herzig S; Henderson NC; Ballabio A; Arany Z; Wolfrum C; Fickert P; Moustafa T", "year": 2026, "journal": "Science Advances", "doi": "10.1126/sciadv.aee1905", "pmid": "42789715", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (liver-specific genetic mTORC1/TFEB manipulation, rapamycin treatment, dietary protein restriction); correlative human MASLD patient cohort", "peer_reviewed": true, "finding": "Establishes a new mTORC1-TFEB/TFE3 signaling axis controlling hepatic bile acid metabolism. Depending on mTORC1 signaling state, mice show coordinated shifts in bile-acid species (non-12-OH vs 12-OH) via altered enzyme expression and cholesterol trafficking; these shifts are reversed by mTORC1 pathway deletion or rapamycin treatment. Dietary protein restriction (which inhibits mTORC1) produces a similar bile-acid shift in mice and correlates with improved metabolic outcomes in human MASLD patients, linking mTORC1 nutrient sensing directly to bile-acid homeostasis and fatty liver disease.", "url": "https://mtor-atlas.org/study/ZAU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZAU2026.json" }, { "sid": "MEN2023", "title": "A bi-steric mTORC1-selective inhibitor overcomes drug resistance in breast cancer", "authors": "Meng D; Bandyopadhyay S et al.", "year": 2023, "journal": "Oncogene", "doi": "10.1038/s41388-023-02737-z", "pmid": "37264081", "pmcid": "PMC10328828", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Human ER+/HER2- breast cancer cell lines; mouse patient-derived xenografts (PDX)", "peer_reviewed": true, "finding": "RMC-6272, a bi-steric molecule with >25-fold selectivity for mTORC1 over mTORC2, completely suppresses mTORC1 (hitting the rapamycin-resistant substrate 4E-BP1) and overcomes hormone- and CDK4/6-inhibitor resistance in breast cancer cell lines and PDX -- the preclinical basis for the RMC-5552 selective-inhibitor clinical program.", "url": "https://mtor-atlas.org/study/MEN2023/", "api_url": "https://mtor-atlas.org/api/v1/studies/MEN2023.json" }, { "sid": "KUB2018", "title": "In Vivo Decoding Mechanisms of the Temporal Patterns of Blood Insulin by the Insulin-AKT Pathway in the Liver", "authors": "Kubota H; Uda S; Matsuzaki F; Yamauchi Y; Kuroda S", "year": 2018, "journal": "Cell Systems", "doi": "10.1016/j.cels.2018.05.013", "pmid": "29960883", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat liver in vivo (hyperinsulinemic-euglycemic clamp with different insulin time patterns) plus mathematical model", "peer_reviewed": true, "finding": "The in-vivo follow-up to KUB2012. In rat liver, all temporal patterns of blood insulin were encoded at the insulin receptor, and downstream molecules decoded them selectively through AKT: S6K read the additional (pulse-like) secretion, G6Pase the basal secretion via FoxO1, GSK3-beta all of it. Modelling tied the selectivity to network structure, sensitivity and time constants. Shows that pattern decoding is not only a cell-culture effect.", "url": "https://mtor-atlas.org/study/KUB2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/KUB2018.json" }, { "sid": "POL2008", "title": "Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration", "authors": "Polak P; Hall MN et al.", "year": 2008, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2008.09.003", "pmid": "19046571", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (adipose raptor KO)", "peer_reviewed": true, "finding": "Adipose raptor knockout yields lean, metabolically protected mice, revealing mTORC1's role in fat metabolism.", "url": "https://mtor-atlas.org/study/POL2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/POL2008.json" }, { "sid": "KIM2008", "title": "Regulation of TORC1 by Rag GTPases in nutrient response", "authors": "Kim E; Guan KL et al.", "year": 2008, "journal": "Nature cell biology", "doi": "10.1038/ncb1753", "pmid": "18604198", "pmcid": "PMC2711503", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Rag GTPases mediate amino-acid signalling to TORC1 (parallel discovery to Sancak 2008).", "url": "https://mtor-atlas.org/study/KIM2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2008.json" }, { "sid": "GUE2006", "title": "Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1", "authors": "Guertin DA; Stevens DM; Thoreen CC; Burds AA; Kalaany NY; Moffat J; Brown M; Fitzgerald KJ; Sabatini DM", "year": 2006, "journal": "Developmental Cell", "doi": "10.1016/j.devcel.2006.10.007", "pmid": "17141160", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Knockout mice (raptor/rictor/mLST8)", "peer_reviewed": true, "finding": "The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice.", "url": "https://mtor-atlas.org/study/GUE2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUE2006.json" }, { "sid": "MADKOUR2026", "title": "Carvedilol attenuates PTZ-induced epileptogenesis: associations with hippocampal neuroinflammation and PI3K/AKT/mTOR-related alterations.", "authors": "Madkour AH; Abdelaziz RR; Nader MA; Elshal M", "year": 2026, "journal": "Scientific Reports", "doi": "10.1038/s41598-026-67306-2", "pmid": "42642481", "pmcid": "PMC13507096", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat (PTZ kindling model)", "peer_reviewed": true, "finding": "Prophylactic carvedilol reduced seizure scores, hippocampal damage and NLRP3-driven neuroinflammation in PTZ-kindled rats, with accompanying changes in PI3K/AKT/mTOR-related protein expression; the authors explicitly state causality was not established.", "url": "https://mtor-atlas.org/study/MADKOUR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MADKOUR2026.json" }, { "sid": "HE2026", "title": "An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline", "authors": "He Y; Pan L; Ping W et al.", "year": 2026, "journal": "Aging Cell", "doi": "10.1111/acel.70671", "pmid": "42605193", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Human cohort (correlation) + mouse (Angptl8-/- knockout, lifespan) + primary adipocyte/cell studies", "peer_reviewed": true, "finding": "Identifies ANGPTL8 as an endocrine driver of adipose-tissue aging: circulating ANGPTL8 tracked with biological age and mortality risk in a large human cohort, and genetic deletion of Angptl8 in mice extended lifespan and reduced senescence markers. Mechanistically, ANGPTL8 binds AKT2 and drives the AKT-mTOR-S6K axis to promote adipocyte senescence; blocking that axis abolished the pro-senescent effect.", "url": "https://mtor-atlas.org/study/HE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HE2026.json" }, { "sid": "HSI2010", "title": "Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E", "authors": "Hsieh AC; Ruggero D et al.", "year": 2010, "journal": "Cancer cell", "doi": "10.1016/j.ccr.2010.01.021", "pmid": "20227039", "pmcid": "PMC2901095", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells; mouse", "peer_reviewed": true, "finding": "Genetic dissection shows the 4E-BP1-eIF4E axis mediates oncogenic mTOR signalling and is druggable.", "url": "https://mtor-atlas.org/study/HSI2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/HSI2010.json" }, { "sid": "GIL2026", "title": "Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study", "authors": "Brooke Gile, Sarojini Bulbule, Mubaraq A Toriola, Brian T Ruan, Shabnam Marium, Anna Benko, Stephanie Grach, Michael Mueller, Lucinda Bateman, Jennifer Bell, Brayden Yellman, Jon Berner, Bela Chheda, David Kaufman, Gunnar Gottschalk, Avik Roy", "year": 2026, "journal": "Journal of Translational Medicine", "doi": "10.1186/s12967-026-08575-3", "pmid": "42432754", "pmcid": "PMC13374298", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (ME/CFS patients)", "peer_reviewed": true, "finding": "In an uncontrolled phase-II pilot (no placebo), low-dose rapamycin was associated with reduced fatigue in ME/CFS. In plasma from responders, purine intermediates shifted, consistent with lower IMP dehydrogenase activity in PBMCs. Lab assays suggest that altered purines can impair mitochondrial metabolism and promote microglial inflammation; these links were not measured in patients.", "url": "https://mtor-atlas.org/study/GIL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/GIL2026.json" }, { "sid": "GAR2003", "title": "Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2", "authors": "Garami A; Thomas G et al.", "year": 2003, "journal": "Molecular cell", "doi": "10.1016/s1097-2765(03)00220-x", "pmid": "12820960", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Drosophila & mammalian cells", "peer_reviewed": true, "finding": "Insulin activates Rheb-GTP, inhibited by TSC1/2, positioning Rheb as the direct upstream activator of TOR.", "url": "https://mtor-atlas.org/study/GAR2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAR2003.json" }, { "sid": "ANC2026", "title": "Strengthening Muscle for Healthy Ageing: Innovative Treatments for Sarcopenia", "authors": "Ancel S; Le Moal E; Wang YX; Blau HM", "year": 2026, "journal": "Nature reviews. Drug discovery", "doi": "10.1038/s41573-026-01514-3", "pmid": "42706321", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": null, "peer_reviewed": true, "finding": "A major pharma-facing review (Blau lab, Stanford/Sanford Burnham) surveying emerging drug strategies for sarcopenia — the age-related loss of muscle mass/strength with no approved therapy. Among the pleiotropic mechanisms discussed, mTORC1 inhibitors are highlighted specifically for their ability to restore impaired autophagy in aging muscle, alongside NAD-related molecules, urolithin A, myostatin inhibitors, SARMs, and 15-PGDH ('gerozyme') inhibitors. Useful high-level context for where mTORC1 modulation sits among competing anti-sarcopenia strategies, though it does not itself address dynamic/temporal mTOR activity.", "url": "https://mtor-atlas.org/study/ANC2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ANC2026.json" }, { "sid": "SIN2013", "title": "Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation", "authors": "Sinclair LV; Cantrell DA et al.", "year": 2013, "journal": "Nature immunology", "doi": "10.1038/ni.2556", "pmid": "23525088", "pmcid": "PMC3672957", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse T cells", "peer_reviewed": true, "finding": "Antigen-receptor-driven System-L (SLC7A5) amino-acid transport controls mTORC1 and T-cell differentiation.", "url": "https://mtor-atlas.org/study/SIN2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/SIN2013.json" }, { "sid": "KRU2010", "title": "Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis", "authors": "Krueger DA et al.", "year": 2010, "journal": "New England Journal of Medicine", "doi": "10.1056/NEJMoa1001671", "pmid": "21047224", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, open-label trial (n=28)", "peer_reviewed": true, "finding": "In patients whose TSC1/TSC2 mutations cause brain tumors, everolimus shrank tumor volume by 30%+ in three-quarters of patients. Open-label and uncontrolled (n=28); randomised confirmation came later (FRA2013).", "url": "https://mtor-atlas.org/study/KRU2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/KRU2010.json" }, { "sid": "SAX2016", "title": "Mechanism of arginine sensing by CASTOR1 upstream of mTORC1", "authors": "Saxton RA; Sabatini DM et al.", "year": 2016, "journal": "Nature", "doi": "10.1038/nature19079", "pmid": "27487210", "pmcid": "PMC4988899", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Structure; cells", "peer_reviewed": true, "finding": "CASTOR1 is a direct arginine sensor upstream of mTORC1; structure reveals the arginine-binding mechanism.", "url": "https://mtor-atlas.org/study/SAX2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAX2016.json" }, { "sid": "SAU2003", "title": "Rheb promotes cell growth as a component of the insulin/TOR signalling network", "authors": "Saucedo LJ; Edgar BA et al.", "year": 2003, "journal": "Nature cell biology", "doi": "10.1038/ncb996", "pmid": "12766776", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Drosophila", "peer_reviewed": true, "finding": "Rheb promotes cell growth as a component of the insulin/TOR network in Drosophila.", "url": "https://mtor-atlas.org/study/SAU2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAU2003.json" }, { "sid": "WANG2026C", "title": "Fluorescent protein ticker tape (FPTT): Multiplexed recording of transcriptional dynamics in living cells and in vivo", "authors": "Wang R; Jiang J et al.", "year": 2026, "journal": "Science Advances", "doi": "10.1126/sciadv.aef9406", "pmid": "42685187", "pmcid": "PMC13537258", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "HEK293T cells, synchronised (live recording of mTOR-driven transcription, SREBP1 response element)", "peer_reviewed": true, "finding": "Engineered a multiplexed fluorescent-protein 'ticker tape' biosensor platform (self-assembling protein fibers + multispectral fluorescent proteins) for longitudinal, single-cell recording of signaling-pathway transcriptional histories (mTOR, NF-κB, STAT3, NFAT, cAMP). Applying the mTOR-FPTT reporter, the authors independently observed cell-cycle-dependent OSCILLATING mTOR activity dynamics -- a new, orthogonal tool corroborating that mTOR signaling is patterned over time rather than static, consistent with JOS2024's cell-cycle oscillation finding.", "url": "https://mtor-atlas.org/study/WANG2026C/", "api_url": "https://mtor-atlas.org/api/v1/studies/WANG2026C.json" }, { "sid": "SUN2026B", "title": "Phosphorylation of OTUB1 promotes autophagy initiation under starvation", "authors": "Sun L; Lian J et al.", "year": 2026, "journal": "Nature Communications", "doi": "10.1038/s41467-026-76796-7", "pmid": "42736303", "pmcid": "PMC13574767", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse (Western diet / MASLD model); cultured cells (starvation)", "peer_reviewed": true, "finding": "Under starvation, ERK phosphorylates the deubiquitinase OTUB1 at S118, which stabilizes it by letting it out-compete TRIM29 for binding to ANXA2. Stabilized OTUB1 upregulates DEPTOR, a natural mTOR inhibitor, which suppresses mTOR and triggers autophagy. In mice, restoring this fasting-triggered ERK-OTUB1-DEPTOR-mTOR axis countered the mTOR-activating effect of a Western diet and eased MASLD (fatty liver disease) progression, giving a mechanistic account of how fasting benefits the liver.", "url": "https://mtor-atlas.org/study/SUN2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/SUN2026B.json" }, { "sid": "ROM2016", "title": "Safety of two-year caloric restriction in non-obese healthy individuals", "authors": "Romashkan SV; Ravussin E et al.", "year": 2016, "journal": "Oncotarget", "doi": "10.18632/oncotarget.8093", "pmid": "26992237", "pmcid": "PMC4991370", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, RCT (CALERIE trial, n=218)", "peer_reviewed": true, "finding": "Two years of sustained 25% caloric restriction in healthy non-obese adults was safe overall, though it lowered bone density more than controls.", "url": "https://mtor-atlas.org/study/ROM2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROM2016.json" }, { "sid": "CHU2019", "title": "Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial", "authors": "Chung CL; Lawrence I; Hoffman M; Elgindi D; Nadhan K; et al.; Sell C", "year": 2019, "journal": "GeroScience", "doi": "10.1007/s11357-019-00113-y", "pmid": "31761958", "pmcid": "PMC6925069", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, RCT (skin, age >40; n=17 completed)", "peer_reviewed": true, "finding": "A small human trial testing whether rapamycin can slow aging in a tissue you can actually see and biopsy - skin. Topical rapamycin significantly lowered the senescence marker p16 and raised collagen VII, with visible improvement in skin appearance. Early, small-scale evidence (17 of 36 completed) that topical rapamycin can reduce a senescence marker in human skin.", "url": "https://mtor-atlas.org/study/CHU2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHU2019.json" }, { "sid": "WEN2026", "title": "Role of Autophagy in Scleral Remodeling During Form-Deprivation Myopia", "authors": "Wen J; Tang S; Zhang Xiaoxiao", "year": 2026, "journal": "FASEB Journal", "doi": "10.1096/fj.202600954RR", "pmid": "42545197", "pmcid": "PMC13431143", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Guinea pig; Human scleral fibroblasts", "peer_reviewed": true, "finding": "Excess scleral autophagy links hypoxic stress to extracellular matrix remodelling in experimental myopia. In form-deprived guinea pigs, subconjunctival rapamycin made myopia worse and 3-MA alleviated it, while atropine slowed myopia and suppressed autophagy-related changes. AMPK/mTOR/P70S6K signalling was measured, but the paper does not establish it as the mediating route.", "url": "https://mtor-atlas.org/study/WEN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/WEN2026.json" }, { "sid": "SCH2025", "title": "The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial", "authors": "Schram AM; Meyerowitz JG et al.", "year": 2025, "journal": "Clinical Cancer Research", "doi": "10.1158/1078-0432.CCR-25-2112", "pmid": "41056387", "pmcid": "PMC12666311", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (Phase 1 dose escalation, n=57, advanced solid tumors, NCT04774952)", "peer_reviewed": true, "finding": "First-in-human, open-label dose-escalation trial (n=57, advanced solid tumors, no comparator arm) of a bi-steric mTORC1-selective inhibitor. Treatment-related hyperglycemia was low (4%) and not dose-limiting, alongside a 64% disease control rate. Because the trial was uncontrolled and made no head-to-head comparison against rapamycin or an ATP-site inhibitor, this is encouraging early clinical evidence consistent with the hypothesis that sparing mTORC2 reduces metabolic toxicity -- it does not establish mTORC2 sparing as the cause.", "url": "https://mtor-atlas.org/study/SCH2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/SCH2025.json" }, { "sid": "JAC2004", "title": "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive", "authors": "Jacinto E; Hall MN et al.", "year": 2004, "journal": "Nature cell biology", "doi": "10.1038/ncb1183", "pmid": "15467718", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC2 (rictor) controls the actin cytoskeleton and is rapamycin-insensitive, defining a second mTOR complex in mammals.", "url": "https://mtor-atlas.org/study/JAC2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/JAC2004.json" }, { "sid": "ROD2016", "title": "Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor", "authors": "Rodrik-Outmezguine VS; Shokat KM et al.", "year": 2016, "journal": "Nature", "doi": "10.1038/nature17963", "pmid": "27279227", "pmcid": "PMC4902179", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells; mouse", "peer_reviewed": true, "finding": "RapaLink-1, a third-generation bivalent inhibitor, overcomes mTOR resistance mutations.", "url": "https://mtor-atlas.org/study/ROD2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROD2016.json" }, { "sid": "TSU2013", "title": "The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1", "authors": "Tsun ZY; Sabatini DM et al.", "year": 2013, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2013.09.016", "pmid": "24095279", "pmcid": "PMC3867817", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "FLCN-FNIP is a GAP for RagC/D; GDP-bound RagC/D is required for the Rag heterodimer to bind mTORC1, promoting its lysosomal recruitment and activation by amino acids.", "url": "https://mtor-atlas.org/study/TSU2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/TSU2013.json" }, { "sid": "MAN2016", "title": "Dynamics of mTORC1 activation in response to amino acids", "authors": "Manifava M; Ktistakis NT et al.", "year": 2016, "journal": "eLife", "doi": "10.7554/eLife.19960", "pmid": "27725083", "pmcid": "PMC5059141", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "HEK293 cells; live imaging of RAPTOR and a fluorescent di-leucine analogue", "peer_reviewed": true, "finding": "Live imaging shows mTORC1 moves to lysosomes within 2 minutes of amino acid addition and peaks by 5 minutes, in step with leucine arriving in lysosomes; phosphorylation of classic mTORC1 targets lags behind, suggesting mTORC1 passes briefly through the lysosome before acting on substrates elsewhere.", "url": "https://mtor-atlas.org/study/MAN2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAN2016.json" }, { "sid": "LEI2018", "title": "Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state", "authors": "Lei HT; Gonen T et al.", "year": 2018, "journal": "Nature structural & molecular biology", "doi": "10.1038/s41594-018-0072-2", "pmid": "29872228", "pmcid": "PMC7346717", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Structure; in vitro", "peer_reviewed": true, "finding": "Crystal structure of arginine-bound SLC38A9 reveals the basis of lysosomal arginine sensing.", "url": "https://mtor-atlas.org/study/LEI2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/LEI2018.json" }, { "sid": "BAS2012", "title": "Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (BOLERO-2)", "authors": "Baselga J; Campone M; Piccart M; Burris HA; Rugo HS; et al.; Hortobagyi GN", "year": 2012, "journal": "New England Journal of Medicine", "doi": "10.1056/NEJMoa1109653", "pmid": "22149876", "pmcid": "PMC5705195", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase 3 RCT (n=724)", "peer_reviewed": true, "finding": "A phase 3 RCT (n=724) proving mTOR matters in a common cancer. Resistance to hormone therapy in breast cancer is associated with mTOR activation. Adding everolimus more than doubled progression-free survival (10.6 vs 4.1 months by central review) - leading to FDA approval. Main toxicity was stomatitis.", "url": "https://mtor-atlas.org/study/BAS2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAS2012.json" }, { "sid": "SHE2019", "title": "Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex", "authors": "Shen K; Sabatini DM et al.", "year": 2019, "journal": "Cell", "doi": "10.1016/j.cell.2019.10.036", "pmid": "31704029", "pmcid": "PMC7008705", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.", "url": "https://mtor-atlas.org/study/SHE2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHE2019.json" }, { "sid": "KAM2000", "title": "Tor-mediated induction of autophagy via an Apg1 protein kinase complex", "authors": "Kamada Y; Funakoshi T; Shintani T; Nagano K; Ohsumi M; Ohsumi Y", "year": 2000, "journal": "J Cell Biol", "doi": "10.1083/jcb.150.6.1507", "pmid": "10995454", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Saccharomyces cerevisiae (yeast)", "peer_reviewed": true, "finding": "The founding experiment of the whole TOR-to-autophagy axis. Starvation or rapamycin raises the kinase activity of Apg1 (the yeast counterpart of ULK1), and TOR keeps autophagy off by holding Apg13 hyperphosphorylated so that it cannot bind and activate Apg1. Boundary: yeast only, and the mammalian version of the same step (ULK1-ATG13-FIP200) was shown separately nine years later.", "url": "https://mtor-atlas.org/study/KAM2000/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAM2000.json" }, { "sid": "KAE2005", "title": "Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients", "authors": "Kaeberlein M; Kennedy BK et al.", "year": 2005, "journal": "Science", "doi": "10.1126/science.1115535", "pmid": "16293764", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast (Saccharomyces cerevisiae)", "peer_reviewed": true, "finding": "A systematic screen of 564 yeast gene deletions found 10 deletions that extend replicative lifespan; genes of the nutrient-responsive TOR and Sch9 pathways were the most frequent hits (6 of 10).", "url": "https://mtor-atlas.org/study/KAE2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAE2005.json" }, { "sid": "SAX2015", "title": "Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway", "authors": "Saxton RA; Wolfson RL; Sabatini DM et al.", "year": 2015, "journal": "Science", "doi": "10.1126/science.aad2087", "pmid": "26586190", "pmcid": "PMC4698039", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines (crystal structure)", "peer_reviewed": true, "finding": "Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor.", "url": "https://mtor-atlas.org/study/SAX2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAX2015.json" }, { "sid": "SHIMADA2026", "title": "Sexual Dimorphism in Placental mTORC1 Signaling, Amino Acid Transport, and Mitochondrial Respiration at Term.", "authors": "Shimada H; Sakuragi T; Zaegel V et al.", "year": 2026, "journal": "Antioxidants", "doi": "10.3390/antiox15080977", "pmid": "42650242", "pmcid": "PMC13509233", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human placenta at term (n=46)", "peer_reviewed": true, "finding": "In 46 term placentas, male placentas showed higher mTORC1 signalling (increased S6RP phosphorylation, reduced 4E-BP1), greater System A amino acid transport and higher mitochondrial respiratory capacity than female placentas, and male pregnancies had a higher birth-weight-to-placental-weight ratio. Observational: a cross-sectional association at a single timepoint, with no intervention and no randomisation, so the direction of the relationship between mTORC1 signalling and growth is not established here and residual confounding by maternal and obstetric factors cannot be excluded.", "url": "https://mtor-atlas.org/study/SHIMADA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHIMADA2026.json" }, { "sid": "LEE2010", "title": "Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies", "authors": "Lee JH; Budanov AV; Bodmer R; Bier E; Karin M et al.", "year": 2010, "journal": "Science", "doi": "10.1126/science.1182228", "pmid": "20203043", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila melanogaster (dSesn loss-of-function)", "peer_reviewed": true, "finding": "An early study linking Sestrin, later identified as a leucine sensor in mammals, to age-associated pathology in flies (fat accumulation, mitochondrial dysfunction, muscle and cardiac decline), prevented by TOR inhibition or AMPK activation. Sestrin sits in a negative feedback loop: TOR activity drives Sestrin expression, and Sestrin inhibits TOR back.", "url": "https://mtor-atlas.org/study/LEE2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/LEE2010.json" }, { "sid": "CHA2014", "title": "The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1", "authors": "Chantranupong L; Sabatini DM et al.", "year": 2014, "journal": "Cell reports", "doi": "10.1016/j.celrep.2014.09.014", "pmid": "25263562", "pmcid": "PMC4223866", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Sestrins bind GATOR2 to negatively regulate amino-acid signalling upstream of mTORC1.", "url": "https://mtor-atlas.org/study/CHA2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHA2014.json" }, { "sid": "EHN2008", "title": "Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis", "authors": "Ehninger D; Silva AJ et al.", "year": 2008, "journal": "Nature medicine", "doi": "10.1038/nm1788", "pmid": "18568033", "pmcid": "PMC2664098", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (Tsc2+/-)", "peer_reviewed": true, "finding": "Rapamycin reverses learning and memory deficits in a Tsc2+/- tuberous sclerosis model.", "url": "https://mtor-atlas.org/study/EHN2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/EHN2008.json" }, { "sid": "KUO1992", "title": "Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase", "authors": "Kuo CJ; Crabtree GR et al.", "year": 1992, "journal": "Nature", "doi": "10.1038/358070a0", "pmid": "1614535", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "T cells; in vitro", "peer_reviewed": true, "finding": "Rapamycin selectively inhibits IL-2-driven activation of p70 S6 kinase during T-cell proliferation.", "url": "https://mtor-atlas.org/study/KUO1992/", "api_url": "https://mtor-atlas.org/api/v1/studies/KUO1992.json" }, { "sid": "GUE2009", "title": "mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice", "authors": "Guertin DA; Sabatini DM et al.", "year": 2009, "journal": "Cancer cell", "doi": "10.1016/j.ccr.2008.12.017", "pmid": "19185849", "pmcid": "PMC2701381", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (prostate)", "peer_reviewed": true, "finding": "mTORC2 is required for prostate cancer driven by Pten loss in mice.", "url": "https://mtor-atlas.org/study/GUE2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUE2009.json" }, { "sid": "INO2006", "title": "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth", "authors": "Inoki K; Guan KL et al.", "year": 2006, "journal": "Cell", "doi": "10.1016/j.cell.2006.06.055", "pmid": "16959574", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "TSC2 integrates Wnt and energy signals through coordinated AMPK and GSK3 phosphorylation.", "url": "https://mtor-atlas.org/study/INO2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/INO2006.json" }, { "sid": "CAN2002", "title": "The phosphoinositide 3-kinase pathway", "authors": "Cantley LC", "year": 2002, "journal": "Science", "doi": "10.1126/science.296.5573.1655", "pmid": "12040186", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review article", "peer_reviewed": true, "finding": "Review establishing PI3K as a central signaling hub controlling cell survival, metabolism, and growth downstream of growth-factor receptors and upstream of Akt and mTOR.", "url": "https://mtor-atlas.org/study/CAN2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAN2002.json" }, { "sid": "CUN2007", "title": "mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex", "authors": "Cunningham JT; Rodgers JT; Arlow DH; Vazquez F; Mootha VK; Puigserver P", "year": 2007, "journal": "Nature", "doi": "10.1038/nature06322", "pmid": "18046414", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Skeletal muscle cells + tissue", "peer_reviewed": true, "finding": "Showed mTOR isn't just about building proteins - it also runs the cell's POWER plants. mTORC1 drives mitochondrial gene expression and oxygen consumption through a YY1-PGC-1alpha transcriptional program; block mTOR with rapamycin and mitochondrial output falls. Explains part of why mTOR inhibition reshapes metabolism.", "url": "https://mtor-atlas.org/study/CUN2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/CUN2007.json" }, { "sid": "YUX2010", "title": "Termination of autophagy and reformation of lysosomes regulated by mTOR", "authors": "Yu L; Lenardo MJ et al.", "year": 2010, "journal": "Nature", "doi": "10.1038/nature09076", "pmid": "20526321", "pmcid": "PMC2920749", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Reactivation of mTOR terminates autophagy and drives autophagic lysosome reformation (ALR).", "url": "https://mtor-atlas.org/study/YUX2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/YUX2010.json" }, { "sid": "GOR2026", "title": "A Systems Pharmacology Model of Aging Identifies Optimal Combination Therapies With Secondary Benefits on Weight Loss and Metabolic Health", "authors": "Goryanin I et al.", "year": 2026, "journal": "CPT Pharmacometrics Syst Pharmacol", "doi": "10.1002/psp4.70322", "pmid": "42572918", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Quantitative systems pharmacology (QSP) model calibrated to human trial data (semaglutide STEP trials)", "peer_reviewed": true, "finding": "A calibrated systems-pharmacology model of aging finds that optimal drug combinations diverge by objective: GLP-1 receptor agonist + SGLT2 inhibitor + metformin is best for metabolic (weight/HbA1c) improvement, while GLP-1 receptor agonist + SGLT2 inhibitor + rapamycin is predicted best for aging-related (frailty/biological-age-gap) benefit — the two goals do not converge on the same regimen. Authors flag the aging predictions as hypothesis-generating, pending external validation.", "url": "https://mtor-atlas.org/study/GOR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/GOR2026.json" }, { "sid": "MAJ2004", "title": "mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways", "authors": "Majumder PK; Sellers WR et al.", "year": 2004, "journal": "Nature medicine", "doi": "10.1038/nm1052", "pmid": "15156201", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (prostate)", "peer_reviewed": true, "finding": "mTOR inhibition (rapamycin/RAD001) reverses Akt-driven prostate intraepithelial neoplasia in mice.", "url": "https://mtor-atlas.org/study/MAJ2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAJ2004.json" }, { "sid": "DEL2011", "title": "The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2", "authors": "Delgoffe GM; Powell JD et al.", "year": 2011, "journal": "Nature immunology", "doi": "10.1038/ni.2005", "pmid": "21358638", "pmcid": "PMC3077821", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "mTORC1 and mTORC2 selectively program distinct CD4 helper T-cell lineages.", "url": "https://mtor-atlas.org/study/DEL2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEL2011.json" }, { "sid": "JIN2026", "title": "Redox-sensitive mTOR-eIF4A signaling promotes selective P-glycoprotein translation.", "authors": "Jin P; Jin M; Feng L; He J; Ying Y; Bai R et al.", "year": 2026, "journal": "Free radical biology & medicine", "doi": "10.1016/j.freeradbiomed.2026.07.033", "pmid": "42468714", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cell line", "peer_reviewed": true, "finding": "Oxidative stress activates a redox-sensitive PI3K-AKT-mTORC1-eIF4A cascade that selectively promotes P-glycoprotein translation via cap-dependent mRNA engagement, revealing a transcription-independent mechanism of rapid multidrug resistance induction.", "url": "https://mtor-atlas.org/study/JIN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/JIN2026.json" }, { "sid": "BAR2016", "title": "Tor forms a dimer through an N-terminal helical solenoid with a complex topology", "authors": "Baretic D; Williams RL et al.", "year": 2016, "journal": "Nature communications", "doi": "10.1038/ncomms11016", "pmid": "27072897", "pmcid": "PMC4833857", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM shows TOR dimerizes through an N-terminal helical solenoid, informing mTORC1 architecture.", "url": "https://mtor-atlas.org/study/BAR2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAR2016.json" }, { "sid": "PIR2026", "title": "Biological limits of lifespan extension: evidence for a shift from pathway leverage to system-level buffering across species", "authors": "Denisa Fv Pirscoveanu, Mihai-Cristian Papa, Britta Kaltwasser, Dirk M Hermann, Ulf Brockmeier, Andrea Cercel, Anthony Oliver, Johannes Gruillari, Marius Viorel Ionica, Aurel Popa-Wagner", "year": 2026, "journal": "Mechanisms of Ageing and Development", "doi": "10.1016/j.mad.2026.112231", "pmid": "42437600", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Multi-species (C. elegans, Drosophila, rodents)", "peer_reviewed": true, "finding": "mTOR/TOR pathway interventions achieve large lifespan extensions in simple organisms but face declining efficacy in mammals due to distributed multi-tissue buffering, redundancy, and pharmacokinetic complexity - proposing a unifying framework for the translational challenge of aging pathway targeting.", "url": "https://mtor-atlas.org/study/PIR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/PIR2026.json" }, { "sid": "WANG2026B", "title": "Pdcd4-Rictor interaction suppresses mTORC2-PFKFB3 axis and tumorigenesis in NSCLC.", "authors": "Wang Q; Xin Y; Zokaei E et al.", "year": 2026, "journal": "Neoplasia", "doi": "10.1016/j.neo.2026.101354", "pmid": "42648032", "pmcid": "PMC13544097", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "NSCLC cell lines; mouse xenograft; human tumour tissue", "peer_reviewed": true, "finding": "Pdcd4 binds Rictor via residues R105/K108/R110 to disrupt mTORC2 assembly and kinase activity, lowering PFKFB3 levels and suppressing glycolysis and NSCLC tumour growth.", "url": "https://mtor-atlas.org/study/WANG2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/WANG2026B.json" }, { "sid": "KEL2024", "title": "Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule", "authors": "Kelly G; Kataura T; Panek J; Ma G; Salmonowicz H; Davis A; Kendall H; Brookes C; et al.; von Zglinicki T; Miwa S; Carroll B; Reynisson J; Korolchuk VI", "year": 2024, "journal": "Developmental cell", "doi": "10.1016/j.devcel.2024.04.020", "pmid": "38897197", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Primary human cells; senescent and naturally aged cells", "peer_reviewed": true, "finding": "Healthy primary human cells run a high level of basal mitophagy, started by mitochondrial superoxide and carried out through the PINK1/Parkin pathway with p62 as the selective receptor. That housekeeping shuts down on entry into senescence and in naturally aged cells. Blocking mitophagy in young proliferating cells was by itself enough to trigger the senescence program, and reactivation of mitophagy was necessary for the anti-senescence effect of rapamycin and of NAD precursors, which places part of rapamycin's action on cellular ageing downstream of mitochondrial quality control rather than beside it. A p62-targeting small molecule restored mitophagy and rescued markers of cellular ageing.", "url": "https://mtor-atlas.org/study/KEL2024/", "api_url": "https://mtor-atlas.org/api/v1/studies/KEL2024.json" }, { "sid": "TID2026", "title": "Genome-wide CRISPRi screen in human iNeurons identifies novel negative mTOR regulator genes associated with focal cortical dysplasia", "authors": "Tidball AM; Luo J; Walker JC; Takla TN; Carvill GL; Parent JM", "year": 2026, "journal": "Neurobiology of Disease", "doi": "10.1016/j.nbd.2026.107602", "pmid": "42731765", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human iPSC-derived neurons (genome-wide CRISPRi screen)", "peer_reviewed": true, "finding": "First unbiased genome-wide functional screen for negative regulators of mTOR signalling carried out in human neurons rather than in cancer lines or non-neural cells. Six genes (LRRC4, EIF3A, TSN, HIP1, PIK3R3, URI1) raise phospho-S6 when knocked down; only PIK3R3 and HIP1 raise phosphorylation across the whole AKT/mTOR/S6 axis, and each of those two has an independently reported candidate pathogenic variant in resected FCD brain tissue, which gives the screen external validity. Boundary: pS6 is a readout of mTORC1 output, not of mTORC1 itself, and four of the six hits did not show pathway-wide hyperphosphorylation, so their placement relative to mTORC1 is unresolved. The screen is in vitro in iPSC-derived neurons; no animal or human causal test of these genes in FCD is included. Relevant to the Atlas as an expansion of the upstream regulator set, and because the GDNF-withdrawal result shows the hits uncouple mTOR output from growth-factor input.", "url": "https://mtor-atlas.org/study/TID2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/TID2026.json" }, { "sid": "GUE2022", "title": "TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle", "authors": "Guerra P; Milias-Argeitis A et al.", "year": 2022, "journal": "Journal of Cell Science", "doi": "10.1242/jcs.260378", "pmid": "35975715", "pmcid": "PMC9658999", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Budding yeast (Saccharomyces cerevisiae), time-lapse single-cell microscopy", "peer_reviewed": true, "finding": "Tracking the localisation of two TORC1 and PKA targets by time-lapse microscopy in hundreds of yeast cells shows that TORC1/PKA activity towards ribosome biogenesis rises and falls in step with the cell cycle even when outside conditions stay constant; mutations in upstream regulators suggest internal metabolic signals partly drive the oscillation.", "url": "https://mtor-atlas.org/study/GUE2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUE2022.json" }, { "sid": "LOE2002", "title": "Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control", "authors": "Loewith R; Hall MN et al.", "year": 2002, "journal": "Molecular cell", "doi": "10.1016/s1097-2765(02)00636-6", "pmid": "12408816", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast S. cerevisiae", "peer_reviewed": true, "finding": "Defined two distinct TOR complexes, only one rapamycin-sensitive, founding the TORC1/TORC2 paradigm.", "url": "https://mtor-atlas.org/study/LOE2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/LOE2002.json" }, { "sid": "BIS2008", "title": "Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis", "authors": "Bissler JJ; Franz DN et al.", "year": 2008, "journal": "The New England journal of medicine", "doi": "10.1056/NEJMoa063564", "pmid": "18184959", "pmcid": "PMC3398441", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (clinical trial)", "peer_reviewed": true, "finding": "Sirolimus shrinks renal angiomyolipomas in tuberous sclerosis / lymphangioleiomyomatosis.", "url": "https://mtor-atlas.org/study/BIS2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/BIS2008.json" }, { "sid": "RAO2026", "title": "An SLC7A5-dependent nutrient-sensing circuit overcomes cisplatin tolerance via mTOR-autophagy signaling.", "authors": "Rao P; Zhang T; Li Ju et al.", "year": 2026, "journal": "Biochemical and Biophysical Research Communications", "doi": "10.1016/j.bbrc.2026.154478", "pmid": null, "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cancer cell lines (genome-wide CRISPR-Cas9 screen)", "peer_reviewed": true, "finding": "A genome-wide CRISPR screen found that mTOR inhibition promotes cisplatin tolerance by activating cytoprotective autophagy — the opposite of the canonical view. SLC7A5 integrates this mTOR-autophagy axis, and leucine supplementation resensitises SLC7A5-expressing tumour cells to cisplatin.", "url": "https://mtor-atlas.org/study/RAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/RAO2026.json" }, { "sid": "SPA2023", "title": "Continuous sensing of nutrients and growth factors by the mTORC1-TFEB axis", "authors": "Sparta B; Albeck JG et al.", "year": 2023, "journal": "eLife", "doi": "10.7554/eLife.74903", "pmid": "37698461", "pmcid": "PMC10547473", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human MCF10A cells (live single-cell imaging, fluorescent TFEB fusions)", "peer_reviewed": true, "finding": "Live imaging of single MCF10A cells shows mTORC1-TFEB signalling adjusts continuously to amino acids and insulin, given alone, one after another or together; at physiological amino acid levels TFEB, AMPK and AKT activity fluctuate in step, and these graded changes track protein synthesis rate through a distributed set of mTORC1 effectors.", "url": "https://mtor-atlas.org/study/SPA2023/", "api_url": "https://mtor-atlas.org/api/v1/studies/SPA2023.json" }, { "sid": "ROC2012", "title": "The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis", "authors": "Roczniak-Ferguson A; Ferguson SM et al.", "year": 2012, "journal": "Science signaling", "doi": "10.1126/scisignal.2002790", "pmid": "22692423", "pmcid": "PMC3437338", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1 phosphorylates TFEB to control lysosomal and autophagy gene transcription.", "url": "https://mtor-atlas.org/study/ROC2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROC2012.json" }, { "sid": "VAL2022", "title": "Structure of the nutrient-sensing hub GATOR2", "authors": "Valenstein ML; Rogala KB; Saxton RA; Chantranupong L; Sabatini DM et al.", "year": 2022, "journal": "Nature", "doi": "10.1038/s41586-022-04939-z", "pmid": "35831510", "pmcid": "PMC9464592", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human GATOR2 complex (cryo-EM)", "peer_reviewed": true, "finding": "Cryo-EM structure of human GATOR2: a 1.1 MDa, two-fold symmetric cage built on an octagonal scaffold decorated with eight pairs of WD40 beta-propellers, and a map of where Sestrin2 and CASTOR1 dock. It substantially advances the GATOR2 side of the sensor module, though how GATOR2 inhibits GATOR1 is still not fully settled.", "url": "https://mtor-atlas.org/study/VAL2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/VAL2022.json" }, { "sid": "ZHOU2026", "title": "TET1-mediated DNA demethylation and transcription activation of MRPS17 induces lung adenocarcinoma through PI3K-AKT-mTOR pathway.", "authors": "Zhou N; Song L; Wu Y et al.", "year": 2026, "journal": "Journal of Molecular Histology", "doi": "10.1007/s10735-026-10862-8", "pmid": "42665721", "pmcid": "PMC13525032", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human LUAD cell lines; mouse xenograft", "peer_reviewed": true, "finding": "TET1 demethylates the MRPS17 promoter to drive MRPS17 overexpression in lung adenocarcinoma, activating PI3K-AKT-mTOR signalling and increasing proliferation, migration and invasion. MRPS17 knockdown induces apoptosis and suppresses tumour growth in vitro and in vivo.", "url": "https://mtor-atlas.org/study/ZHOU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHOU2026.json" }, { "sid": "SCH2003", "title": "TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function", "authors": "Schalm SS; Blenis J et al.", "year": 2003, "journal": "Current biology : CB", "doi": "10.1016/s0960-9822(03)00329-4", "pmid": "12747827", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro", "peer_reviewed": true, "finding": "The TOS motif mediates raptor binding and controls multisite 4E-BP1 phosphorylation by mTORC1.", "url": "https://mtor-atlas.org/study/SCH2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/SCH2003.json" }, { "sid": "GAR2009", "title": "Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)", "authors": "Garcia-Martinez JM; Alessi DR et al.", "year": 2009, "journal": "The Biochemical journal", "doi": "10.1042/BJ20090489", "pmid": "19402821", "pmcid": "PMC2708931", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro; cells", "peer_reviewed": true, "finding": "Ku-0063794 is a specific ATP-competitive mTOR inhibitor blocking mTORC1 and mTORC2.", "url": "https://mtor-atlas.org/study/GAR2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAR2009.json" }, { "sid": "CAO2026", "title": "Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome", "authors": "Cao ZL; Zhao SC; Lin F; Liu YH; Hong XT; Hong LY; Xu LQ; Li FP; Yu HY; Yao WG; Chen WY", "year": 2026, "journal": "Frontiers in Oncology", "doi": "10.3389/fonc.2026.1848740", "pmid": "42558438", "pmcid": "PMC13437482", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Narrative synthesis (human genetics + mouse mechanistic data)", "peer_reviewed": true, "finding": "Reframes Birt-Hogg-Dube (BHD) syndrome beyond the classic 'global mTORC1 hyperactivation' model: FLCN acts as a GAP for RagC/D, giving substrate-selective (not global) mTORC1 control. Biallelic FLCN loss drives kidney tumors via MiT/TFE nuclear accumulation, while haploinsufficiency alone is sufficient for lung and skin lesions -- resolving the 'mTORC1 paradox' via gene dosage and signaling timing. Narrative synthesis of human genetics and mouse mechanistic data.", "url": "https://mtor-atlas.org/study/CAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAO2026.json" }, { "sid": "VEZ1975", "title": "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle", "authors": "Vezina C; Kudelski A; Sehgal SN", "year": 1975, "journal": "Journal of Antibiotics", "doi": "10.7164/antibiotics.28.721", "pmid": "1102508", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Streptomyces hygroscopicus (soil bacterium)", "peer_reviewed": true, "finding": "The original isolation of rapamycin from a soil bacterium found on Easter Island, discovered first as an antifungal compound decades before its mTOR-inhibiting mechanism was known.", "url": "https://mtor-atlas.org/study/VEZ1975/", "api_url": "https://mtor-atlas.org/api/v1/studies/VEZ1975.json" }, { "sid": "YAN2013", "title": "mTOR kinase structure, mechanism and regulation", "authors": "Yang H; Rudge DG; Koos JD; Vaidialingam B; Yang HJ; Pavletich NP", "year": 2013, "journal": "Nature", "doi": "10.1038/nature12122", "pmid": "23636326", "pmcid": "PMC4512754", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "X-ray crystallography (structural biology)", "peer_reviewed": true, "finding": "Solved the crystal structure of the mTOR kinase itself. Revealed why the active site is so hard to reach - it sits in a deep recess guarded by the FRB domain, which acts as a 'gatekeeper' letting substrates in. This structure explains at the atomic level exactly how FKBP12-rapamycin blocks access, and why activating cancer mutations cluster where they do.", "url": "https://mtor-atlas.org/study/YAN2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAN2013.json" }, { "sid": "MCNEILL2026", "title": "Sirolimus is effective for paediatric Evans syndrome and secondary autoimmune cytopenias: A retrospective cohort study.", "authors": "McNeill M; Cellarius C; Illamperuma N et al.", "year": 2026, "journal": "British Journal of Haematology", "doi": "10.1111/bjh.70795", "pmid": "42655953", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (paediatric retrospective cohort)", "peer_reviewed": true, "finding": "Retrospective single-centre paediatric cohort reporting that sirolimus is effective in paediatric Evans syndrome and secondary autoimmune cytopenias. Abstract not yet indexed — effect sizes to be confirmed.", "url": "https://mtor-atlas.org/study/MCNEILL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MCNEILL2026.json" }, { "sid": "LI2026B", "title": "Brucella suis vaccine strain 2 promotes intracellular proliferation by inducing M2 macrophage polarization and autophagy through PI3K/Akt/mTOR signalling.", "authors": "Li H; Yang J; Xu T; Ji Z; Wang Zhenhai", "year": 2026, "journal": "Journal of Medical Microbiology", "doi": "10.1099/jmm.0.002182", "pmid": "42658194", "pmcid": "PMC13521125", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "BV2 murine microglial cells", "peer_reviewed": true, "finding": "Brucella suis vaccine strain 2 drives mixed M1/M2 macrophage polarisation and autophagic activation in BV2 cells; the M2 state and autophagy synergistically promote intracellular bacterial replication through PI3K/Akt/mTOR signalling.", "url": "https://mtor-atlas.org/study/LI2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/LI2026B.json" }, { "sid": "WOL2017", "title": "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1", "authors": "Wolfson RL; Sabatini DM et al.", "year": 2017, "journal": "Nature", "doi": "10.1038/nature21423", "pmid": "28199306", "pmcid": "PMC5360989", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "KICSTOR tethers GATOR1 to the lysosome, required for nutrient control of mTORC1.", "url": "https://mtor-atlas.org/study/WOL2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/WOL2017.json" }, { "sid": "BET2013", "title": "mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology", "authors": "Betz C; Hall MN et al.", "year": 2013, "journal": "Proceedings of the National Academy of Sciences of the United States of America", "doi": "10.1073/pnas.1302455110", "pmid": "23852728", "pmcid": "PMC3732980", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC2-Akt signalling localizes to mitochondria-associated ER membranes to regulate mitochondrial function.", "url": "https://mtor-atlas.org/study/BET2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/BET2013.json" }, { "sid": "OSH2007", "title": "The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1", "authors": "Oshiro N; Yonezawa K et al.", "year": 2007, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.M702636200", "pmid": "17517883", "pmcid": "PMC3199301", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "PRAS40 is a physiological raptor-bound substrate and inhibitor of mTORC1.", "url": "https://mtor-atlas.org/study/OSH2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/OSH2007.json" }, { "sid": "RAV2004", "title": "Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease", "authors": "Ravikumar B; Rubinsztein DC et al.", "year": 2004, "journal": "Nature Genetics", "doi": "10.1038/ng1362", "pmid": "15146184", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila and mouse models of Huntington's disease", "peer_reviewed": true, "finding": "Induced autophagy cleared toxic clumped proteins and improved symptoms in fly (rapamycin) and mouse (the rapalog CCI-779) models of Huntington's disease.", "url": "https://mtor-atlas.org/study/RAV2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/RAV2004.json" }, { "sid": "HEN2026", "title": "Survival and Homeostasis of Alveolar Macrophages in Vivo Depend on mTOR Signaling", "authors": "Hennessy-Strahs S; Su X; Sun S; Deng G; Muo W; Li Jiarui; Miller T; Xiao X; Li XC", "year": 2026, "journal": "American Journal of Respiratory Cell and Molecular Biology", "doi": "10.1093/ajrcmb/aanag139", "pmid": "42578718", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (myeloid-specific Mtor deletion); GM-CSF-driven alveolar-macrophage-like cell culture (in vitro)", "peer_reviewed": true, "finding": "Myeloid-specific deletion of mTOR (and pharmacologic mTOR inhibition with temsirolimus) causes progressive depletion of alveolar macrophages, impaired phagocytosis, lipid accumulation and PAP-like lung pathology in mice, identifying mTOR as a nonredundant regulator of alveolar macrophage survival — mechanistic support for mTOR-inhibitor-associated pulmonary toxicity.", "url": "https://mtor-atlas.org/study/HEN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HEN2026.json" }, { "sid": "ZHOU2026B", "title": "Corilagin attenuates osteoarthritis progression by coordinating NF-κB inhibition with PI3K/AKT/mTOR-associated autophagy restoration.", "authors": "Zhou R; Li Jie; Chen S et al.", "year": 2026, "journal": "International Immunopharmacology", "doi": "10.1016/j.intimp.2026.117342", "pmid": "42664894", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (DMM OA model); primary mouse chondrocytes", "peer_reviewed": true, "finding": "Corilagin restores chondrocyte autophagic flux and ECM synthesis by inhibiting PI3K/AKT/mTOR and NF-κB signalling, reducing cartilage erosion and OARSI scores in the mouse DMM osteoarthritis model.", "url": "https://mtor-atlas.org/study/ZHOU2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHOU2026B.json" }, { "sid": "TAO2026", "title": "Impaired mTOR/SREBP1-Mediated Lipogenesis as a Mechanism of Hepatic Glycogen Accumulation in a Carnivorous Fish Model, Largemouth Bass (Micropterus salmoides)", "authors": "Tao J; Chen S; Liu N; Gong Y; Zhang S; He J; Huang X; Chen N; Li S", "year": 2026, "journal": "FASEB Journal", "doi": "10.1096/fj.202602519R", "pmid": "42606523", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Carnivorous fish (hepatic glycogen accumulation model)", "peer_reviewed": true, "finding": "mTOR/SREBP1 signaling governs hepatic glucose partitioning; the insulin-responsive mTOR/SREBP1 axis promotes lipogenesis versus glycogen accumulation. In this model -- a carnivorous fish -- impairment of the axis is associated with hepatic glycogen overload mimicking glucose intolerance.", "url": "https://mtor-atlas.org/study/TAO2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/TAO2026.json" }, { "sid": "MCC2011", "title": "Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES)", "authors": "McCormack FX; Inoue Y; Moss J; Singer LG; Strange C; et al.; Trapnell BC", "year": 2011, "journal": "New England Journal of Medicine", "doi": "10.1056/NEJMoa1100391", "pmid": "21410393", "pmcid": "PMC3118601", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, RCT (n=89, women with LAM)", "peer_reviewed": true, "finding": "A landmark placebo-controlled RCT (n=89) - the first to show that rapamycin (sirolimus) benefits a human lung disease. In LAM, lung function normally declines relentlessly; sirolimus STOPPED that decline while patients took it (and it resumed after stopping). Randomised human evidence that mTOR inhibition can suspend progression of this disease; the benefit did not persist after withdrawal.", "url": "https://mtor-atlas.org/study/MCC2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/MCC2011.json" }, { "sid": "BOD2001", "title": "Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo", "authors": "Bodine SC; Yancopoulos GD et al.", "year": 2001, "journal": "Nature cell biology", "doi": "10.1038/ncb1101-1014", "pmid": "11715023", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse; muscle", "peer_reviewed": true, "finding": "Akt/mTOR signalling is necessary and sufficient to drive skeletal-muscle hypertrophy and counteract atrophy in vivo.", "url": "https://mtor-atlas.org/study/BOD2001/", "api_url": "https://mtor-atlas.org/api/v1/studies/BOD2001.json" }, { "sid": "DIB2012", "title": "TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1", "authors": "Dibble CC; Manning BD et al.", "year": 2012, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2012.06.009", "pmid": "22795129", "pmcid": "PMC3693578", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "TBC1D7 is the third core subunit of the TSC1-TSC2 complex regulating Rheb/mTORC1.", "url": "https://mtor-atlas.org/study/DIB2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/DIB2012.json" }, { "sid": "BIT2016", "title": "Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice", "authors": "Bitto A; Kaeberlein M et al.", "year": 2016, "journal": "eLife", "doi": "10.7554/eLife.16351", "pmid": "27549339", "pmcid": "PMC4996648", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (middle-aged)", "peer_reviewed": true, "finding": "In male mice, a 3-month rapamycin course started in middle age increased life expectancy by up to 60% (high injected dose). In females that dose did not extend lifespan and shifted cancers toward aggressive haematopoietic types; a lower dietary dose raised survival in both sexes.", "url": "https://mtor-atlas.org/study/BIT2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/BIT2016.json" }, { "sid": "THO2009", "title": "An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1", "authors": "Thoreen CC; Kang SA; Chang JW; Liu Q; Zhang Jianming; Gao Y; Reichling LJ; Sim T; Sabatini DM; Gray NS", "year": 2009, "journal": "Journal of Biological Chemistry", "doi": "10.1074/jbc.M900301200", "pmid": "19150980", "pmcid": "PMC2658096", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse/human cells", "peer_reviewed": true, "finding": "Dropped a bombshell: rapamycin does NOT fully block mTORC1. Using Torin1 (which jams the active site directly), the authors showed rapamycin leaves important mTORC1 jobs running - notably 4E-BP1 phosphorylation and autophagy suppression. This reframed a decade of rapamycin experiments and launched the search for complete inhibitors.", "url": "https://mtor-atlas.org/study/THO2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/THO2009.json" }, { "sid": "NAZ2026", "title": "Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation", "authors": "Nazemi M; Yanes B; Vancauwenberghe E; Oyelade I; Walker H; Rainero E", "year": 2026, "journal": "PLoS Biology", "doi": "10.1371/journal.pbio.3003555", "pmid": "42758789", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human breast and pancreatic cancer cell lines (2D/3D culture)", "peer_reviewed": true, "finding": "Collagen I drives alpha2beta1 integrin-dependent mTORC1/S6 activation and membrane localization of the LAT1-4F2hc amino acid transporter, sustaining essential amino acid supply and cancer cell survival in nutrient-poor, collagen-rich tumor stroma; LAT1-4F2hc is upregulated in basal-like breast/pancreatic tumors and correlates with poor prognosis.", "url": "https://mtor-atlas.org/study/NAZ2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/NAZ2026.json" }, { "sid": "LI2026", "title": "GPR143, a novel immunohistochemical marker for renal tumors with FLCN/TSC/MTOR-TFE alterations.", "authors": "Li Q, Singh A, Hu R, Huang J, Shapiro JB", "year": 2026, "journal": "Virchows Archiv", "doi": "10.1007/s00428-026-04646-4", "pmid": "42463886", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human tissue (renal tumor specimens)", "peer_reviewed": true, "finding": "GPR143 is a sensitive and specific immunohistochemical biomarker for renal tumors driven by FLCN/TSC/MTOR-TFE pathway alterations, offering a practical diagnostic tool beyond existing ancillary tests.", "url": "https://mtor-atlas.org/study/LI2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LI2026.json" }, { "sid": "LAM2012", "title": "Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity", "authors": "Lamming DW et al.; Sabatini DM", "year": 2012, "journal": "Science", "doi": "10.1126/science.1215135", "pmid": "22461615", "pmcid": "PMC3324089", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Side effect", "model_system": "Mouse (in vivo glucose and insulin tolerance)", "peer_reviewed": true, "finding": "In mice, chronic rapamycin also disrupts mTORC2, causing insulin resistance; reduced mTORC1 signalling alone (female mTOR/mLST8 double-heterozygous mice) extended lifespan without impairing glucose homeostasis.", "url": "https://mtor-atlas.org/study/LAM2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAM2012.json" }, { "sid": "BAR2013", "title": "A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1", "authors": "Bar-Peled L; Chantranupong L; Cherniack AD; Chen WW; Ottina KA; Grabiner BC; Spear ED; Carter SL; Meyerson M; Sabatini DM", "year": 2013, "journal": "Science", "doi": "10.1126/science.1232044", "pmid": "23723238", "pmcid": "PMC3728654", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + cancer genomics", "peer_reviewed": true, "finding": "Found the OFF switch for amino acid signaling: the GATOR1 complex is a GAP that shuts the Rag GTPases (and thus mTORC1) down when amino acids run low, while GATOR2 opposes it. GATOR1 genes are mutated in cancers, making those tumors 'blind' to starvation and hypersensitive to rapamycin.", "url": "https://mtor-atlas.org/study/BAR2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAR2013.json" }, { "sid": "MARCHANT2026", "title": "Constitutive mTORC1 Activation in Skeletal Muscle Increases Inflammation but is not Sufficient to Impair Glucose Tolerance.", "authors": "Marchant ED; Kalenta H; Kilroe SP; May J; Martini WZ; Weldon KS et al.", "year": 2026, "journal": "Function (Oxford, England)", "doi": "10.1152/function.039.2026", "pmid": "42468920", "pmcid": "PMC13459988", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Constitutive mTORC1 activation in mouse skeletal muscle (via GATOR1 complex KO) increases inflammatory markers but is not sufficient to impair glucose tolerance, indicating that additional metabolic inputs beyond muscle mTORC1 hyperactivation are required to drive glucose intolerance.", "url": "https://mtor-atlas.org/study/MARCHANT2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MARCHANT2026.json" }, { "sid": "CHE2018", "title": "Cryo-EM structure of human mTOR complex 2", "authors": "Chen Xizi; Xu Y et al.", "year": 2018, "journal": "Cell research", "doi": "10.1038/s41422-018-0029-3", "pmid": "29567957", "pmcid": "PMC5951902", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM structure of human mTORC2 defines its subunit organization and substrate access.", "url": "https://mtor-atlas.org/study/CHE2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHE2018.json" }, { "sid": "SET2012", "title": "A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB", "authors": "Settembre C; Ballabio A et al.", "year": 2012, "journal": "The EMBO journal", "doi": "10.1038/emboj.2012.32", "pmid": "22343943", "pmcid": "PMC3298007", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "A lysosome-to-nucleus mechanism uses mTOR-dependent TFEB phosphorylation to sense lysosomal state.", "url": "https://mtor-atlas.org/study/SET2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/SET2012.json" }, { "sid": "RAM2018", "title": "mTOR signaling regulates central and peripheral circadian clock function", "authors": "Ramanathan C; Kathale ND; Liu D; Lee C; Freeman DA; Hogenesch JB; Cao R; Liu AC", "year": 2018, "journal": "PLoS Genetics", "doi": "10.1371/journal.pgen.1007369", "pmid": "29750810", "pmcid": "PMC5965903", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Hepatocyte and adipocyte clock models; Tsc2-/- fibroblasts; ex vivo SCN and liver; mTOR heterozygous mice", "peer_reviewed": true, "finding": "mTOR sets how fast and how strongly the circadian clock ticks. Inhibiting mTOR lengthened the clock period and flattened its amplitude; activating it shortened the period and raised the amplitude, in cells, in ex vivo brain (SCN) and liver clocks, and in mTOR heterozygous mice, whose locomotor rhythm ran longer. The study starts from the observation that mTOR activity itself oscillates over 24 hours in many tissues.", "url": "https://mtor-atlas.org/study/RAM2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/RAM2018.json" }, { "sid": "ANA2019", "title": "Architecture of human Rag GTPase heterodimers and their complex with mTORC1", "authors": "Anandapadamanaban M; Williams RL et al.", "year": 2019, "journal": "Science", "doi": "10.1126/science.aax3939", "pmid": "31601764", "pmcid": "PMC6795536", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Structures of Rag GTPase heterodimers with mTORC1 explain nucleotide-state-dependent recruitment.", "url": "https://mtor-atlas.org/study/ANA2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/ANA2019.json" }, { "sid": "LON2005", "title": "Rheb binds and regulates the mTOR kinase", "authors": "Long X; Avruch J et al.", "year": 2005, "journal": "Current biology : CB", "doi": "10.1016/j.cub.2005.02.053", "pmid": "15854902", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro", "peer_reviewed": true, "finding": "Rheb binds the mTOR kinase domain and directly stimulates its activity.", "url": "https://mtor-atlas.org/study/LON2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/LON2005.json" }, { "sid": "SHI2014", "title": "Making new contacts: the mTOR network in metabolism and signalling crosstalk", "authors": "Shimobayashi M; Hall MN et al.", "year": 2014, "journal": "Nature reviews. Molecular cell biology", "doi": "10.1038/nrm3757", "pmid": "24556838", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of the mTOR network in metabolism and signalling crosstalk.", "url": "https://mtor-atlas.org/study/SHI2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHI2014.json" }, { "sid": "JOH2013", "title": "mTOR is a key modulator of ageing and age-related disease", "authors": "Johnson SC; Rabinovitch PS; Kaeberlein M", "year": 2013, "journal": "Nature", "doi": "10.1038/nature11861", "pmid": "23325216", "pmcid": "PMC3687363", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review (multi-species synthesis)", "peer_reviewed": true, "finding": "The landmark Nature review that put mTOR at the center of aging biology. Lays out the case that inhibiting mTOR extends lifespan across species and guards against a growing list of age-related diseases - while being candid that side effects currently block its use in healthy people. Excellent orientation map for the whole field.", "url": "https://mtor-atlas.org/study/JOH2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/JOH2013.json" }, { "sid": "DRU2009", "title": "Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis", "authors": "Drummond MJ; Rasmussen BB et al.", "year": 2009, "journal": "Journal of Physiology", "doi": "10.1113/jphysiol.2008.163816", "pmid": "19188252", "pmcid": "PMC2678224", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, controlled trial", "peer_reviewed": true, "finding": "Rapamycin given before resistance exercise completely blocked the normal post-exercise increase in human muscle protein synthesis.", "url": "https://mtor-atlas.org/study/DRU2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/DRU2009.json" }, { "sid": "PAU2025", "title": "Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry", "authors": "Paul D; Cappell SD et al.", "year": 2025, "journal": "Nature", "doi": "10.1038/s41586-025-09328-w", "pmid": "40739344", "pmcid": "PMC12488482", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells entering the cell cycle after mitogen stimulation", "peer_reviewed": true, "finding": "After mitogen stimulation, mTOR quickly phosphorylates the APC/C adaptor CDH1, partly releasing it and briefly inactivating APC/C; the glycolytic enzyme PFKFB3 accumulates and glycolysis rises, until a delayed phosphatase restores APC/C. This incoherent feed-forward loop produces a pulse of glycolysis that cell cycle entry requires.", "url": "https://mtor-atlas.org/study/PAU2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/PAU2025.json" }, { "sid": "LIP2015", "title": "The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation", "authors": "Lipton JO; Yuan ED; Boyle LM; Ebrahimi-Fakhari D; Kwiatkowski E; Nathan A; Güttler T; Davis F; Asara JM; Sahin M", "year": 2015, "journal": "Cell", "doi": "10.1016/j.cell.2015.04.002", "pmid": "25981667", "pmcid": "PMC4447213", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse tissues and cultured cells", "peer_reviewed": true, "finding": "S6K1, a main output of mTORC1, phosphorylates the clock protein BMAL1 rhythmically, and that phosphorylation lets BMAL1 join the translation machinery and drive protein synthesis. Protein synthesis rates oscillated over the day in a BMAL1-dependent way. A direct molecular bridge between mTORC1 output and the 24-hour clock.", "url": "https://mtor-atlas.org/study/LIP2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIP2015.json" }, { "sid": "DAN2026", "title": "Recurrent reversible mutations in gaf1 driving metastable TORC1 inhibitor resistance in fission yeast", "authors": "Dan L; Ye X; Liu S; Zhang J; Qiang Z; Yang X; Li W", "year": 2026, "journal": "Microbiology Spectrum", "doi": "10.1128/spectrum.01467-26", "pmid": "42752201", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Fission yeast (Schizosaccharomyces pombe)", "peer_reviewed": true, "finding": "Metastable resistance to TORC1 inhibitors (rapamycin plus caffeine) in fission yeast is driven by recurrent, spontaneously reversible loss-of-function mutations in gaf1, a GATA transcription factor and negative growth regulator downstream of TORC1 - a genetic (not epigenetic) toggle that can silently contaminate lab yeast stocks.", "url": "https://mtor-atlas.org/study/DAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DAN2026.json" }, { "sid": "NEF2013", "title": "Rapamycin extends murine lifespan but has limited effects on aging", "authors": "Neff F; Ehninger D et al.", "year": 2013, "journal": "The Journal of clinical investigation", "doi": "10.1172/JCI67674", "pmid": "23863708", "pmcid": "PMC3726163", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Rapamycin extends murine lifespan but has only limited effects on classic aging phenotypes.", "url": "https://mtor-atlas.org/study/NEF2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/NEF2013.json" }, { "sid": "YANG2026", "title": "Early-life exposure to polypropylene microplastics and DEHP induces ASD-relevant neurodevelopmental alterations involving mTOR-regulated autophagy impairment", "authors": "Yang G; Gong C; Zheng X; Chen H; Wang Y; Zhang H; Hu F; Wan J; Zhu Z; Sun X; Zhang L; Li R", "year": 2026, "journal": "Ecotoxicology and Environmental Safety", "doi": "10.1016/j.ecoenv.2026.120659", "pmid": "42600301", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (ICR, early-life exposure model)", "peer_reviewed": true, "finding": "PP-MPs and DEHP activate mTOR and impair autophagy, inducing ASD-like neurodevelopmental deficits in mice; rapamycin rescues autophagic flux and social/behavioral phenotypes.", "url": "https://mtor-atlas.org/study/YANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/YANG2026.json" }, { "sid": "FOK2014", "title": "Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome", "authors": "Fok WC; Richardson A et al.", "year": 2014, "journal": "PloS one", "doi": "10.1371/journal.pone.0083988", "pmid": "24409289", "pmcid": "PMC3883653", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Rapamycin-fed mice show extended lifespan with major changes in the liver transcriptome.", "url": "https://mtor-atlas.org/study/FOK2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/FOK2014.json" }, { "sid": "WAG2014", "title": "Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib", "authors": "Wagle N; Rosenberg JE et al.", "year": 2014, "journal": "Cancer discovery", "doi": "10.1158/2159-8290.CD-13-0353", "pmid": "24625776", "pmcid": "PMC4122326", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (patient)", "peer_reviewed": true, "finding": "Two concurrent activating MTOR mutations are implicated in an extraordinary clinical response to rapalog therapy. Single-patient observation: hypothesis-generating, not evidence of a general response predictor.", "url": "https://mtor-atlas.org/study/WAG2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/WAG2014.json" }, { "sid": "KAL2010", "title": "Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner", "authors": "Kalender A; Selvaraj A; Thomas G; Kozma SC et al.", "year": 2010, "journal": "Cell Metabolism", "doi": "10.1016/j.cmet.2010.03.014", "pmid": "20444419", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells (AMPK-null and TSC1/2-null)", "peer_reviewed": true, "finding": "Metformin inhibits mTORC1 even in cells lacking AMPK or TSC1/TSC2, and the effect requires the Rag GTPases instead. Together with Foretz 2010 this places a large part of metformin's action outside the AMPK axis it is usually credited to.", "url": "https://mtor-atlas.org/study/KAL2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAL2010.json" }, { "sid": "REB2015", "title": "SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1", "authors": "Rebsamen M; Superti-Furga G et al.", "year": 2015, "journal": "Nature", "doi": "10.1038/nature14107", "pmid": "25561175", "pmcid": "PMC4376665", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SLC38A9 is a component of the lysosomal amino-acid sensing machinery controlling mTORC1.", "url": "https://mtor-atlas.org/study/REB2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/REB2015.json" }, { "sid": "WEI2008", "title": "The TSC-mTOR signaling pathway regulates the innate inflammatory response", "authors": "Weichhart T; Saemann MD et al.", "year": 2008, "journal": "Immunity", "doi": "10.1016/j.immuni.2008.08.012", "pmid": "18848473", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse/human monocytes", "peer_reviewed": true, "finding": "The TSC-mTOR pathway controls the innate inflammatory response of monocytes/macrophages.", "url": "https://mtor-atlas.org/study/WEI2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/WEI2008.json" }, { "sid": "NOR2026", "title": "Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations", "authors": "Nordbeck AJ; Martá-Ariza M; Ek Olofsson H; Kanshin E; Ueberheide B et al.", "year": 2026, "journal": "Alzheimer's & Dementia", "doi": "10.1002/alz.71776", "pmid": "42635110", "pmcid": "PMC13501503", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human post-mortem hippocampus (Down syndrome with AD neuropathology vs neurotypical controls)", "peer_reviewed": true, "finding": "Spatial transcriptomics plus localized proteomics on human post-mortem hippocampus show that mTOR pathway signalling is significantly altered in specific hippocampal subfields in Down syndrome with Alzheimer's disease neuropathology, while insulin pathway signalling is altered specifically in dentate granule neurons — pointing to subregion- and cell-type-specific mTOR/insulin dysregulation rather than a uniform whole-tissue shift. Explicitly framed by the authors as preliminary.", "url": "https://mtor-atlas.org/study/NOR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/NOR2026.json" }, { "sid": "SCA2020", "title": "The 3.2-A resolution structure of human mTORC2", "authors": "Scaiola A; Maier T et al.", "year": 2020, "journal": "Science advances", "doi": "10.1126/sciadv.abc1251", "pmid": "33158864", "pmcid": "PMC7673708", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "The 3.2 A cryo-EM structure of human mTORC2 pinpoints Rictor's C-terminus as the source of rapamycin insensitivity.", "url": "https://mtor-atlas.org/study/SCA2020/", "api_url": "https://mtor-atlas.org/api/v1/studies/SCA2020.json" }, { "sid": "WUX2013", "title": "Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression", "authors": "Wu JJ; Finkel T et al.", "year": 2013, "journal": "Cell reports", "doi": "10.1016/j.celrep.2013.07.030", "pmid": "23994476", "pmcid": "PMC3784301", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (mTOR hypomorph)", "peer_reviewed": true, "finding": "Genetically reduced mTOR increases mouse lifespan with tissue-specific slowing of aging.", "url": "https://mtor-atlas.org/study/WUX2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/WUX2013.json" }, { "sid": "OKI2021", "title": "Imaging dynamic mTORC1 pathway activity in vivo reveals marked shifts that support time-specific inhibitor therapy in AML", "authors": "Oki T; Scadden DT et al.", "year": 2021, "journal": "Nature Communications", "doi": "10.1038/s41467-020-20491-8", "pmid": "33431855", "pmcid": "PMC7801403", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse AML model; intravital imaging of bone marrow with fluorescent probes", "peer_reviewed": true, "finding": "Fluorescent probes imaged in the bone marrow of live mice show mTORC1 activity in AML cells falls as the disease progresses but is high at the moment of maximal chemotherapy response, where it is induced rather than selected; inhibiting mTORC1 at that time improved killing of AML cells.", "url": "https://mtor-atlas.org/study/OKI2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/OKI2021.json" }, { "sid": "POW2006", "title": "Extension of chronological life span in yeast by decreased TOR pathway signaling", "authors": "Powers RW; Fields S et al.", "year": 2006, "journal": "Genes & development", "doi": "10.1101/gad.1381406", "pmid": "16418483", "pmcid": "PMC1356109", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast (S. cerevisiae)", "peer_reviewed": true, "finding": "Decreased TOR pathway signalling extends chronological lifespan in yeast.", "url": "https://mtor-atlas.org/study/POW2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/POW2006.json" }, { "sid": "SAB1995", "title": "Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells", "authors": "Sabers CJ; Abraham RT et al.", "year": 1995, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.270.2.815", "pmid": "7822316", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Rat/mouse cells; in vitro", "peer_reviewed": true, "finding": "Isolated mTOR as the FKBP12-rapamycin-associated protein controlling G1-S progression.", "url": "https://mtor-atlas.org/study/SAB1995/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAB1995.json" }, { "sid": "ZHO2015", "title": "Dynamic Visualization of mTORC1 Activity in Living Cells", "authors": "Zhou X; Clister TL; Lowry PR; Seldin MM; Wong GW; Zhang J", "year": 2015, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2015.02.031", "pmid": "25772363", "pmcid": "PMC4567530", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cell lines (live-cell FRET imaging, subcellularly targeted reporter)", "peer_reviewed": true, "finding": "TORCAR, the first genetically encoded FRET reporter of mTORC1 activity, lets mTORC1 be watched in living cells as it changes. It showed mTORC1 activity not only at the lysosome but also in the cytosol, nucleus and at the plasma membrane; growth factor spread activity widely, while a leucine surrogate kept it at the lysosome and nucleus. A growth-factor-induced calcium transient contributed to mTORC1 activity. The earliest live reader of mTORC1 held in the atlas.", "url": "https://mtor-atlas.org/study/ZHO2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHO2015.json" }, { "sid": "SAN2007", "title": "PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase", "authors": "Sancak Y; Thoreen CC; Peterson TR; Lindquist RA; Kang SA; Spooner E; Carr SA; Sabatini DM", "year": 2007, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2007.03.003", "pmid": "17386266", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (biochemistry)", "peer_reviewed": true, "finding": "Identified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can fully switch mTORC1 on. Explained how hormone signals set the exact strength of mTORC1 activity.", "url": "https://mtor-atlas.org/study/SAN2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAN2007.json" }, { "sid": "STR2022", "title": "Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice", "authors": "Strong R; Miller RA; Cheng CJ; Nelson JF; Gelfond J; Harrison DE et al.", "year": 2022, "journal": "Aging Cell", "doi": "10.1111/acel.13724", "pmid": "36179270", "pmcid": "PMC9741502", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Genetically heterogeneous UM-HET3 mice, three test sites (ITP C2017 cohort)", "peer_reviewed": null, "finding": "NIA Interventions Testing Program C2017 cohort. In MALE mice, rapamycin plus acarbose started at 9 months produced a longer lifespan than either of the two prior ITP cohorts treated with rapamycin alone, suggesting the combination is more potent than its components used separately. In FEMALES the combination was neither better nor worse than rapamycin alone, which the authors relate to the limited survival benefit acarbose alone had shown in earlier female cohorts. Captopril gave a small but significant lifespan increase in females (4-5%). CAVEAT (important for how this is cited): the rapamycin-only comparison is HISTORICAL, against prior cohorts, not a concurrent rapamycin-only arm in the same experiment, so 'more potent than either component' is the authors' suggestion rather than a within-experiment randomised comparison.", "url": "https://mtor-atlas.org/study/STR2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/STR2022.json" }, { "sid": "HSU2011", "title": "The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling", "authors": "Hsu PP; Sabatini DM et al.", "year": 2011, "journal": "Science", "doi": "10.1126/science.1199498", "pmid": "21659604", "pmcid": "PMC3177140", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTOR-dependent phosphoproteomics reveal Grb10 as a substrate mediating feedback inhibition of PI3K.", "url": "https://mtor-atlas.org/study/HSU2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/HSU2011.json" }, { "sid": "INO2003", "title": "TSC2 mediates cellular energy response to control cell growth and survival", "authors": "Inoki K; Zhu T; Guan KL", "year": 2003, "journal": "Cell", "doi": "10.1016/s0092-8674(03)00929-2", "pmid": "14651849", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells (biochemistry)", "peer_reviewed": true, "finding": "Established the energy-sensing arm of the pathway. When energy runs low, AMPK phosphorylates TSC2, boosting its ability to shut mTOR down - protecting the cell from burning through resources and from starvation-induced death. The founding paper for how mTOR reads the cell's fuel gauge (complements the Akt-TSC2 growth-factor arm).", "url": "https://mtor-atlas.org/study/INO2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/INO2003.json" }, { "sid": "SWA2026", "title": "Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition", "authors": "Swarup A; Kuhs RA; Hardman VU; Howard KL; Subbaraman S; Bolger TA", "year": 2026, "journal": "The Journal of Biological Chemistry", "doi": "10.1016/j.jbc.2026.113580", "pmid": "42759659", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Saccharomyces cerevisiae (ded1-mam mutant) and medulloblastoma-relevant reporter assays", "peer_reviewed": true, "finding": "Medulloblastoma-associated DDX3X mutations, modeled in the yeast ortholog Ded1 (ded1-mam), cause rapamycin-resistant growth and selectively upregulate translation of unstructured-5'UTR pro-growth transcripts after TORC1 inhibition, a mechanism by which mutant DDX3X may let tumor cells bypass TORC1-dependent stress/growth control.", "url": "https://mtor-atlas.org/study/SWA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SWA2026.json" }, { "sid": "WIL2012", "title": "Rapamycin slows aging in mice", "authors": "Wilkinson JE; Burmeister L; Brooks SV; Chan CC; Friedline S; Harrison DE; Hejtmancik JF; Nadon N; Strong R; Wood LK; Woodward MA; Miller RA", "year": 2012, "journal": "Aging Cell", "doi": "10.1111/j.1474-9726.2012.00832.x", "pmid": "22587563", "pmcid": "PMC3434687", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Genetically heterogeneous mice", "peer_reviewed": true, "finding": "Answered a crucial objection: does rapamycin really slow AGING, or just prevent the cancers that kill mice? By showing slower age-related change across many tissues (heart, liver, tendon, activity), it argued for genuine slowing of aging. Honestly reported harms too - more cataracts and testicular degeneration - making it a balanced landmark, not hype.", "url": "https://mtor-atlas.org/study/WIL2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/WIL2012.json" }, { "sid": "HOX2019", "title": "The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism", "authors": "Hoxhaj G; Manning BD et al.", "year": 2019, "journal": "Nature reviews. Cancer", "doi": "10.1038/s41568-019-0216-7", "pmid": "31686003", "pmcid": "PMC7314312", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of the PI3K-AKT-mTOR network at the interface of oncogenic signalling and metabolism.", "url": "https://mtor-atlas.org/study/HOX2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/HOX2019.json" }, { "sid": "WYA2017", "title": "mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient", "authors": "Wyant GA; Sabatini DM et al.", "year": 2017, "journal": "Cell", "doi": "10.1016/j.cell.2017.09.046", "pmid": "29053970", "pmcid": "PMC5704964", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SLC38A9 effluxes essential amino acids (e.g. leucine) from lysosomes to activate mTORC1.", "url": "https://mtor-atlas.org/study/WYA2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/WYA2017.json" }, { "sid": "SPI2010", "title": "Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease", "authors": "Spilman P; Podlutskaya N; Hart MJ; Debnath J; Gorostiza O; Bredesen D; Richardson A; Strong R; Galvan V", "year": 2010, "journal": "PLoS ONE", "doi": "10.1371/journal.pone.0009979", "pmid": "20376313", "pmcid": "PMC2848616", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "PDAPP transgenic mice (Alzheimer's model)", "peer_reviewed": true, "finding": "Connected the longevity drug to a specific age-related disease. Long-term rapamycin prevented memory deficits and lowered toxic amyloid-beta in an Alzheimer's mouse model - and the benefit tracked with INCREASED autophagy in neurons. Suggested that the same autophagy boost that may slow aging could also help clear disease-causing proteins.", "url": "https://mtor-atlas.org/study/SPI2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/SPI2010.json" }, { "sid": "HUANG2026", "title": "Recurrent PIK3CA-E545K mutation promotes cervical cancer growth and invasion via AKT/mTOR signaling.", "authors": "Huang C; Zhang W; Ma X; Li X; Sun X", "year": 2026, "journal": "Molecular genetics and genomics", "doi": "10.1007/s00438-026-02495-z", "pmid": "42562966", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human (cancer cell lines + xenograft)", "peer_reviewed": true, "finding": "PIK3CA-E545K hotspot mutation enhances cervical cancer cell proliferation and invasion by activating AKT/mTOR signaling, validated in xenograft models.", "url": "https://mtor-atlas.org/study/HUANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HUANG2026.json" }, { "sid": "ROB2013", "title": "Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis", "authors": "Robitaille AM; Hall MN et al.", "year": 2013, "journal": "Science", "doi": "10.1126/science.1228771", "pmid": "23429704", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Quantitative phosphoproteomics show mTORC1 activates de novo pyrimidine synthesis.", "url": "https://mtor-atlas.org/study/ROB2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROB2013.json" }, { "sid": "MUT2026", "title": "ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation", "authors": "Muthukottiappan P; Winter D et al.", "year": 2026, "journal": "bioRxiv (preprint)", "doi": "10.64898/2026.03.31.715514", "pmid": null, "pmcid": null, "evidence": { "code": "PP", "label": "Preprint, not peer-reviewed", "note": "this describes the kind of study, not its quality" }, "category": "Preprint", "model_system": "Human cell lines", "peer_reviewed": false, "finding": "Identifies a new layer of control over mTORC1's lysosomal machinery: cholesterol exchange between the ER and lysosome regulates lysosome movement via mTOR-dependent phosphorylation of LAMTOR1, a core component of the Ragulator complex that anchors the Rag GTPases already in this Atlas.", "url": "https://mtor-atlas.org/study/MUT2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MUT2026.json" }, { "sid": "ROM2001", "title": "Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways", "authors": "Rommel C; Bodine SC et al.", "year": 2001, "journal": "Nature Cell Biology", "doi": "10.1038/ncb1101-1009", "pmid": "11715022", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cultured muscle cells (mouse)", "peer_reviewed": true, "finding": "Shows IGF-1 drives muscle fiber hypertrophy through Akt, via both the mTOR and GSK3 branches, in cultured myotubes, establishing mTOR as a central node for muscle growth signaling.", "url": "https://mtor-atlas.org/study/ROM2001/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROM2001.json" }, { "sid": "SUX2017", "title": "Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex", "authors": "Su MY; Hurley JH et al.", "year": 2017, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2017.10.016", "pmid": "29107538", "pmcid": "PMC5722659", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Hybrid structure", "peer_reviewed": true, "finding": "Hybrid structural model of the RagA/C-Ragulator mTORC1 activation complex.", "url": "https://mtor-atlas.org/study/SUX2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/SUX2017.json" }, { "sid": "LEE2024", "title": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review", "authors": "Lee DJW; Hodzic Kuerec A; Maier AB", "year": 2024, "journal": "Lancet Healthy Longevity", "doi": "10.1016/S2666-7568(23)00258-1", "pmid": "38310895", "pmcid": null, "evidence": { "code": "S", "label": "Synthesis of human data", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Systematic review (19 human studies, 5 databases)", "peer_reviewed": true, "finding": "The first systematic review of rapamycin/rapalogs in humans for aging. Screened 18,400 articles, included 19 studies. Found improvements in immune, cardiovascular, and skin (integumentary) parameters; NO significant effect on endocrine, muscular, or neurological systems. No serious adverse events in healthy people, but more infections and raised cholesterol/triglycerides in people with age-related disease. This is the highest-tier human-evidence summary in the whole Atlas - it aggregates many individual human studies rather than reporting one.", "url": "https://mtor-atlas.org/study/LEE2024/", "api_url": "https://mtor-atlas.org/api/v1/studies/LEE2024.json" }, { "sid": "ZHAI2026", "title": "Pungenin Promotes Hair Growth in Mouse Models of Androgenic Alopecia Through Transcriptional Regulation of the PI3K/AKT/mTOR Axis.", "authors": "Zhai W; Yang J; Zhang L et al.", "year": 2026, "journal": "Molecules", "doi": "10.3390/molecules31162864", "pmid": "42653946", "pmcid": "PMC13515395", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (DHT-induced AGA); primary mouse hair follicle cells", "peer_reviewed": true, "finding": "Topical pungenin accelerated hair regrowth in DHT-induced androgenetic alopecia mice, reducing type II 5α-reductase expression and modulating PI3K/AKT/FoxO/mTOR transcriptional signalling in hair follicle cells.", "url": "https://mtor-atlas.org/study/ZHAI2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHAI2026.json" }, { "sid": "HAFEZ2026", "title": "Melittin attenuates imiquimod-induced psoriatic dermatitis in mice: a role for autophagy activation via PI3K/Akt/mTOR pathway suppression.", "authors": "Hafez SA; Ahmed AA; Elkhoely A; Ahmed AAE", "year": 2026, "journal": "Saudi pharmaceutical journal", "doi": "10.1007/s44446-026-00105-y", "pmid": "42560464", "pmcid": "PMC13447632", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (psoriasis model)", "peer_reviewed": true, "finding": "Melittin (bee venom, 80 mg/kg i.p.) reduces psoriatic dermatitis severity by 60% in an imiquimod mouse model by suppressing PI3K/Akt/mTOR signaling and activating autophagy.", "url": "https://mtor-atlas.org/study/HAFEZ2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAFEZ2026.json" }, { "sid": "CUI2023", "title": "Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex", "authors": "Cui Z; Napolitano G; de Araujo MEG; Esposito A; Monfregola J; Huber LA; Ballabio A; Hurley JH", "year": 2023, "journal": "Nature", "doi": "10.1038/s41586-022-05652-7", "pmid": "36697823", "pmcid": "PMC9931586", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure (human proteins, cell-free reconstitution)", "peer_reviewed": true, "finding": "First structural view of how mTORC1 actually reaches TFEB to phosphorylate it: two full Rag-Ragulator complexes present a single TFEB molecule to the mTOR active site, one in the normal Raptor-docking arrangement and a second, non-canonical one that grips TFEB's own first helix. Mutating that grip point drives TFEB straight into the nucleus (turning on autophagy/lysosome genes) without disturbing where mTORC1 itself sits. Explains, at the level of atoms, why TFEB phosphorylation needs the tumour suppressor FLCN and the GDP-loaded state of RagC in a way no other mTORC1 substrate does. Boundary: cryo-EM of a complex reconstituted from purified human proteins — a static structural snapshot, not a live cell or a real-time measurement.", "url": "https://mtor-atlas.org/study/CUI2023/", "api_url": "https://mtor-atlas.org/api/v1/studies/CUI2023.json" }, { "sid": "MOE2025", "title": "Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results", "authors": "Moel M; Harinath G; Lee V; Nyquist A; Morgan SL; Isman A; Zalzala S", "year": 2025, "journal": "Aging (Albany NY)", "doi": "10.18632/aging.206235", "pmid": "40188830", "pmcid": "PMC12074816", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, RCT, ages 50-85 (n=114 completed)", "peer_reviewed": true, "finding": "First completed long-term RCT of rapamycin for healthy human aging (NCT04488601, 48 weeks, n=114). Primary endpoint (visceral fat by DXA) showed NO significant change (p=0.942) - a null result on the pre-registered primary endpoint. Secondary endpoints were more promising: women on the 10mg/week dose had significant improvements in lean tissue mass and self-reported pain. A textbook example of why the pre-registered primary endpoint, not the most exciting secondary finding, is what should drive the headline conclusion.", "url": "https://mtor-atlas.org/study/MOE2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/MOE2025.json" }, { "sid": "EIS2009", "title": "Induction of autophagy by spermidine promotes longevity", "authors": "Eisenberg T; Knauer H; Schauer A; Buettner S; Ruckenstuhl C; Carmona-Gutierrez D; Ring J; Schroeder S; Magnes C; Antonacci L; Fussi H; Deszcz L; Hartl R; Schraml E; Criollo A; Megalou E; Weiskopf D; Laun P; Heeren G; Breitenbach M; Grubeck-Loebenstein B; Herker E; Fahrenkrog B; Froehlich KU; Sinner F; Tavernarakis N; Minois N; Kroemer G; Madeo F", "year": 2009, "journal": "Nat Cell Biol", "doi": "10.1038/ncb1975", "pmid": "19801973", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Yeast, Drosophila, C. elegans, mice, human immune cells", "peer_reviewed": true, "finding": "The opening paper of the caloric-restriction-mimetic branch: a natural polyamine whose level falls with human age extends lifespan in yeast, flies, worms and human immune cells, and the effect depends on autophagy. In ageing yeast this works through inhibition of histone acetyltransferases, which raises autophagy gene expression. The paper did not measure mTOR, so whether this route bypasses mTOR is not tested here. Boundary: no mammalian lifespan data in this paper.", "url": "https://mtor-atlas.org/study/EIS2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/EIS2009.json" }, { "sid": "FLY2013", "title": "Late-life rapamycin treatment reverses age-related heart dysfunction", "authors": "Flynn JM; O'Leary MN; Zambataro CA; Academia EC; Presley MP; et al.; Melov S", "year": 2013, "journal": "Aging Cell", "doi": "10.1111/acel.12109", "pmid": "23734717", "pmcid": "PMC4098908", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Aged (24-month) female mice", "peer_reviewed": true, "finding": "Striking evidence that in mice mTOR inhibition doesn't just SLOW aging - it can partly reverse an established age-related phenotype. Giving rapamycin to already-old (24-month) female mice for 3 months improved aged heart function, reversing or attenuating age-related cardiac changes, with RNA-seq changes suggesting anti-hypertrophic and anti-inflammatory effects. Started late, still worked.", "url": "https://mtor-atlas.org/study/FLY2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/FLY2013.json" }, { "sid": "ZHO2009", "title": "Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice", "authors": "Zhou J; Parada LF et al.", "year": 2009, "journal": "The Journal of neuroscience", "doi": "10.1523/JNEUROSCI.5685-08.2009", "pmid": "19211884", "pmcid": "PMC3904448", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (Pten KO)", "peer_reviewed": true, "finding": "In neural Pten-knockout mice, rapamycin prevented and reversed neuronal hypertrophy and improved a subset of the PTEN-associated abnormal behaviours.", "url": "https://mtor-atlas.org/study/ZHO2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHO2009.json" }, { "sid": "FOR2010", "title": "Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state", "authors": "Foretz M; Hebrard S; Andreelli F; Viollet B et al.", "year": 2010, "journal": "The Journal of Clinical Investigation", "doi": "10.1172/JCI40671", "pmid": "20577053", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (liver-specific AMPK-null and LKB1-null); primary hepatocytes", "peer_reviewed": true, "finding": "The paper that broke the simple 'metformin works through AMPK' story. Metformin still suppressed hepatic glucose production in mice and hepatocytes lacking AMPK or LKB1, acting instead through a fall in hepatic energy charge. Any claim that metformin's benefit is AMPK-mediated has to answer this result.", "url": "https://mtor-atlas.org/study/FOR2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/FOR2010.json" }, { "sid": "VEL2003", "title": "Genetics: influence of TOR kinase on lifespan in C. elegans", "authors": "Vellai T et al.", "year": 2003, "journal": "Nature", "doi": "10.1038/426620a", "pmid": "14668850", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Caenorhabditis elegans (RNAi)", "peer_reviewed": true, "finding": "Silencing the single worm TOR gene roughly doubled C. elegans lifespan, showing the longevity role of TOR inhibition is conserved across an enormous evolutionary distance.", "url": "https://mtor-atlas.org/study/VEL2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/VEL2003.json" }, { "sid": "JAC2026", "title": "Diet-dependent, beneficial and adverse effects of rapamycin on life span of Drosophila melanogaster", "authors": "Jackson LN; Boles AM; Frye CT; Patel IA; Mockett RJ", "year": 2026, "journal": "GeroScience", "doi": "10.1007/s11357-026-02372-y", "pmid": "42570192", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila melanogaster (5 fly strains)", "peer_reviewed": true, "finding": "Rapamycin's effect on Drosophila lifespan is highly diet-dependent: on a cornmeal/torula-yeast medium it was harmful in 19 of 26 experiments across 5 strains, but on a nutrient-rich brewer's-yeast medium it was beneficial in 8 and neutral in 14, with no significant harm. Effects on median lifespan ranged from -51.3% to +5.4%, varying by sex and strain; rapamycin was also toxic to development at 10-200 µM.", "url": "https://mtor-atlas.org/study/JAC2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/JAC2026.json" }, { "sid": "NAZ2013", "title": "mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6", "authors": "Nazio F; Cecconi F et al.", "year": 2013, "journal": "Nature cell biology", "doi": "10.1038/ncb2708", "pmid": "23524951", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTOR restrains autophagy by controlling ULK1 ubiquitylation and stability via AMBRA1/TRAF6.", "url": "https://mtor-atlas.org/study/NAZ2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/NAZ2013.json" }, { "sid": "SAX2026", "title": "Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial", "authors": "Saxena A; Drew CJ; Cannings-John R; Pickles T; Mills LJ; Sampson JR et al.", "year": 2026, "journal": "Journal of medical genetics", "doi": "10.1136/jmg-2026-111529", "pmid": "42562625", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (TSC patients, aged 16-60, RCT)", "peer_reviewed": true, "finding": "In a multicentre RCT of TSC patients (n=38 randomised, 2:1 everolimus:placebo), 24 weeks of everolimus produced similarly large 'responder' rates for neuropsychological improvement as placebo (87% vs 75%), suggesting large practice/placebo effects rather than a clear drug benefit on cognition -- despite everolimus's established efficacy for TSC tumours and epilepsy. Adverse events were more frequent with everolimus (88% vs 61.5%).", "url": "https://mtor-atlas.org/study/SAX2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAX2026.json" }, { "sid": "RAUCH2026", "title": "Tankyrase-2 regulates adipocyte differentiation through AMPK/mTOR signaling.", "authors": "Rauch B; Ujlaki G; Poliska S; Murahwa N; Kovacs P; et al.", "year": 2026, "journal": "The FEBS journal", "doi": "10.1111/febs.70676", "pmid": "42563506", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cell line (adipocytes)", "peer_reviewed": true, "finding": "Deleting TNKS1 or TNKS2 slows adipocyte differentiation, with inhibited autophagy, AMPK activation and suppressed mTORC1; the TNKS2-knockout defect is rescued by NV-5138 or by LKB1 inhibition, and TNKS2 ADP-ribosylates LKB1 (cell line).", "url": "https://mtor-atlas.org/study/RAUCH2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/RAUCH2026.json" }, { "sid": "KAP2004", "title": "Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway", "authors": "Kapahi P et al.", "year": 2004, "journal": "Current Biology", "doi": "10.1016/j.cub.2004.03.059", "pmid": "15186745", "pmcid": "PMC2754830", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila melanogaster", "peer_reviewed": true, "finding": "Genetically reducing TOR pathway activity extends fruit fly lifespan, overlapping with dietary restriction effects.", "url": "https://mtor-atlas.org/study/KAP2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAP2004.json" }, { "sid": "WAN2015", "title": "Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1", "authors": "Wang S; Sabatini DM et al.", "year": 2015, "journal": "Science", "doi": "10.1126/science.1257132", "pmid": "25567906", "pmcid": "PMC4295826", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "The lysosomal transporter SLC38A9 signals arginine sufficiency to mTORC1.", "url": "https://mtor-atlas.org/study/WAN2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/WAN2015.json" }, { "sid": "SHIM2026", "title": "D-Amino Acid Prodrug DLMEH Activates mTORC1 via Sestrin2 to Restore Muscle Protein Synthesis in Sarcopenia.", "authors": "Shim JH; Lee JY; Ahn BK; Woo SW; Han J; Kim HS", "year": 2026, "journal": "Molecular Therapy", "doi": "10.1016/j.ymthe.2026.09.007", "pmid": "42723280", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat (dexamethasone-induced muscle atrophy); human primary myotubes", "peer_reviewed": true, "finding": "DLMEH, a D-leucine ester prodrug, binds Sestrin2 with leucine-like potency (Kd 28.3 uM, equivalent to L-leucine) and activates mTORC1 in a Sestrin2-dependent way. It restored protein synthesis in human myotubes and preserved muscle mass, grip strength and endurance in a rat dexamethasone-induced atrophy model (not an ageing sarcopenia model).", "url": "https://mtor-atlas.org/study/SHIM2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHIM2026.json" }, { "sid": "CAR2008", "title": "Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer", "authors": "Carracedo A; Pandolfi PP et al.", "year": 2008, "journal": "The Journal of clinical investigation", "doi": "10.1172/JCI34739", "pmid": "18725988", "pmcid": "PMC2518073", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells", "peer_reviewed": true, "finding": "mTORC1 inhibition activates the MAPK pathway via a PI3K-dependent feedback loop in cancer.", "url": "https://mtor-atlas.org/study/CAR2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAR2008.json" }, { "sid": "CHA2016", "title": "The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway", "authors": "Chantranupong L; Scaria SM; Saxton RA; Gygi MP; Shen K; Wyant GA; Wang T; Harper JW; Gygi SP; Sabatini DM", "year": 2016, "journal": "Cell", "doi": "10.1016/j.cell.2016.02.035", "pmid": "26972053", "pmcid": "PMC4808398", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (biochemistry)", "peer_reviewed": true, "finding": "Identified CASTOR1 as the direct arginine sensor: when arginine binds CASTOR1, it lets go of GATOR2, switching mTORC1 on. Together with Sestrin2 (leucine) this built the picture of mTORC1 as a cell that literally tastes individual amino acids.", "url": "https://mtor-atlas.org/study/CHA2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHA2016.json" }, { "sid": "DIB2015", "title": "Regulation of mTORC1 by PI3K signaling", "authors": "Dibble CC; Cantley LC et al.", "year": 2015, "journal": "Trends in cell biology", "doi": "10.1016/j.tcb.2015.06.002", "pmid": "26159692", "pmcid": "PMC4734635", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of mTORC1 regulation by PI3K signalling.", "url": "https://mtor-atlas.org/study/DIB2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/DIB2015.json" }, { "sid": "NOL2026", "title": "Rapamycin across biology and medicine: From molecular mechanisms to clinical and translational frontiers", "authors": "Nolasco LNRA; de Vargas Wolfgramm Dos Santos E; Dos Reis Trabach RS; Meira DD; Louro ID", "year": 2026, "journal": "Biochimica et Biophysica Acta, General Subjects", "doi": "10.1016/j.bbagen.2026.131009", "pmid": "42785697", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Narrative review (no primary experimental model)", "peer_reviewed": true, "finding": "Comprehensive review tracing rapamycin from its discovery as an antifungal macrolide to its identification as the founding mTOR inhibitor. Covers mTOR's role integrating nutrient/growth-factor/stress signals, established and emerging clinical applications of rapamycin/rapalogs, limitations and adverse effects of mTOR inhibition, and translational prospects for using mTOR inhibition to prevent or delay chronic disease and extend healthspan.", "url": "https://mtor-atlas.org/study/NOL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/NOL2026.json" }, { "sid": "DAB2026", "title": "mTORC1 inhibition upregulates CD20 and enhances anti-CD20 antibody efficacy in B-cell precursor acute lymphoblastic leukemia", "authors": "Dąbkowska A, Janowska M, Pastorczak A, Domka K, Nowicka Z, Urbanska Z, Zając W, Bugajewski M, Grzybowska J, Pruchniak P, Fidyt K, Fendler W, Taslim J, Crump NT, Ushmorov A, Patkowska E, Firczuk M", "year": 2026, "journal": "Leukemia", "doi": "10.1038/s41375-026-03093-z", "pmid": "42618701", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "BCP-ALL cell lines; patient-derived and in vivo models", "peer_reviewed": true, "finding": "mTORC1 inhibitors upregulate CD20 via the AKT-FOXO1 axis and promote B-lineage maturation in B-cell precursor ALL, enhancing the antitumor efficacy of anti-CD20 monoclonal antibodies -- including in high-risk IKZF1-deleted disease -- providing a rationale for combining mTORC1 inhibition with CD20-directed immunotherapy.", "url": "https://mtor-atlas.org/study/DAB2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DAB2026.json" }, { "sid": "DIB2013", "title": "Signal integration by mTORC1 coordinates nutrient input with biosynthetic output", "authors": "Dibble CC; Manning BD et al.", "year": 2013, "journal": "Nature cell biology", "doi": "10.1038/ncb2763", "pmid": "23728461", "pmcid": "PMC3743096", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review: mTORC1 integrates nutrient input with biosynthetic output.", "url": "https://mtor-atlas.org/study/DIB2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/DIB2013.json" }, { "sid": "ULL2026", "title": "FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer", "authors": "Ullern H; Johannessen JA; Kasikci F; Formica M; Karimi Melve N; Andresen S; Brech A; Axcrona K; Jørgensen K; Farkas L; Enserink JM; Knævelsrud H", "year": 2026, "journal": "Autophagy Reports", "doi": "10.1080/27694127.2026.2705631", "pmid": "42569319", "pmcid": "PMC13449739", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "BHD patient-derived kidney cancer cell line; Norwegian BHD patient tumor cohort", "peer_reviewed": true, "finding": "In BHD patient-derived kidney cancer cells, FLCN loss causes constitutive nuclear TFEB localization and mTORC1 hyperactivation, but leaves bulk autophagy flux and LC3 lipidation unaffected; however, the autophagy receptor SQSTM1/p62 accumulates in enlarged puncta, a finding replicated in a Norwegian cohort of BHD patient kidney tumors, showing p62 accumulation is dissociable from bulk autophagic flux.", "url": "https://mtor-atlas.org/study/ULL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ULL2026.json" }, { "sid": "KAH2000", "title": "Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study", "authors": "Kahan BD (Rapamune US Study Group)", "year": 2000, "journal": "Lancet", "doi": "10.1016/S0140-6736(00)02480-6", "pmid": "10963197", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase III RCT (n=719)", "peer_reviewed": true, "finding": "The trial that established rapamycin (sirolimus) as an immunosuppressant in kidney transplant patients - its original, still-standard clinical use.", "url": "https://mtor-atlas.org/study/KAH2000/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAH2000.json" }, { "sid": "ROB2012", "title": "TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO", "authors": "Robida-Stubbs S; Blackwell TK et al.", "year": 2012, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2012.04.007", "pmid": "22560223", "pmcid": "PMC3348514", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "C. elegans", "peer_reviewed": true, "finding": "In C. elegans, genetic TORC1 inhibition extends lifespan through SKN-1/Nrf and DAF-16/FoxO, whereas rapamycin's lifespan effect requires SKN-1 but not DAF-16, apparently because it also hits TORC2.", "url": "https://mtor-atlas.org/study/ROB2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROB2012.json" }, { "sid": "MIL2011", "title": "Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice", "authors": "Miller RA; Harrison DE et al.", "year": 2011, "journal": "J Gerontol A Biol Sci Med Sci", "doi": "10.1093/gerona/glq178", "pmid": "20974732", "pmcid": "PMC3021372", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Negative_result", "model_system": "Mouse (genetically heterogeneous, ITP, 3 sites)", "peer_reviewed": true, "finding": "In the same experimental design that showed rapamycin extended median lifespan by 10-18%, neither resveratrol nor simvastatin had any significant effect on survival - a direct head-to-head negative control run at the same time, in the same mice.", "url": "https://mtor-atlas.org/study/MIL2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/MIL2011.json" }, { "sid": "SEL2009", "title": "Ribosomal protein S6 kinase 1 signaling regulates mammalian life span", "authors": "Selman C; Withers DJ et al.", "year": 2009, "journal": "Science", "doi": "10.1126/science.1177221", "pmid": "19797661", "pmcid": "PMC4954603", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (S6K1 knockout)", "peer_reviewed": true, "finding": "Deleting S6K1 (a direct mTORC1 effector) extended lifespan in FEMALE mice (+19% median); the effect was not significant in males. It also protected against age-related bone, immune and motor decline. One of the clearest cases of the sex dimorphism catalogued in gap H6 - and a reminder that a single downstream branch, not mTORC1 as a whole, can carry much of the ageing signal.", "url": "https://mtor-atlas.org/study/SEL2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/SEL2009.json" }, { "sid": "YAO2011", "title": "Everolimus for advanced pancreatic neuroendocrine tumors (RADIANT-3)", "authors": "Yao JC; Shah MH; Ito T; Bohas CL; Wolin EM; et al.; Oberg K", "year": 2011, "journal": "New England Journal of Medicine", "doi": "10.1056/NEJMoa1009290", "pmid": "21306238", "pmcid": "PMC4208619", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase 3 RCT (n=410)", "peer_reviewed": true, "finding": "A phase 3 RCT (n=410) that made everolimus a standard treatment for pancreatic neuroendocrine tumors. It more than doubled progression-free survival (11.0 vs 4.6 months, a 65% reduction in risk of progression/death) with mostly mild side effects. Another FDA-approved indication built on blocking mTOR.", "url": "https://mtor-atlas.org/study/YAO2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAO2011.json" }, { "sid": "LAW2018", "title": "A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold", "authors": "Lawrence RE; Zoncu R et al.", "year": 2018, "journal": "Nature cell biology", "doi": "10.1038/s41556-018-0148-6", "pmid": "30061680", "pmcid": "PMC6279252", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "A nutrient-induced affinity switch in the Rag-Ragulator scaffold controls mTORC1 lysosomal recruitment.", "url": "https://mtor-atlas.org/study/LAW2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAW2018.json" }, { "sid": "MAT2017", "title": "Caloric restriction improves health and survival of rhesus monkeys", "authors": "Mattison JA et al.", "year": 2017, "journal": "Nature Communications", "doi": "10.1038/ncomms14063", "pmid": "28094793", "pmcid": "PMC5247583", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rhesus macaque (2 independent cohorts)", "peer_reviewed": true, "finding": "Direct comparison of two long-term primate CR studies (NIA, Wisconsin) supports consistent health benefits; the survival effect depended on study design and control-diet composition.", "url": "https://mtor-atlas.org/study/MAT2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAT2017.json" }, { "sid": "WAN2026", "title": "Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila", "authors": "Wang J; Cai Z; Gu J; Xiong S; Yi J; Yang M; Chang K; Ning X; Wen Y; Yan Y; Lu J; Wang Y; Zhai Z", "year": 2026, "journal": "Nature", "doi": "10.1038/s41586-026-11029-x", "pmid": "42778591", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila melanogaster — Lsp2 genetic ablation, lifespan assay, translatomic (ribosome profiling) analysis", "peer_reviewed": true, "finding": "Identifies Lsp2, a Drosophila fat-body storage protein, as an amino-acid-induced feedback activator of mTORC1 that specifically boosts translation of TOP-motif mRNAs (mostly ribosomal proteins) via 4E-BP — a rapamycin-resistant arm of mTORC1 output. Genetic loss of Lsp2 reduces TOP mRNA translation and robustly extends lifespan without cost to reproduction, revealing a rapamycin-independent route from mTORC1 activity to organismal longevity.", "url": "https://mtor-atlas.org/study/WAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/WAN2026.json" }, { "sid": "YAN2026", "title": "SLC15A3-mediated dipeptide metabolism confers antimetabolite resistance in lymphoma via mTORC1 activation.", "authors": "Yang H; Zingaro VA; Boardman K; Noronha A; Guney E; et al.; Ruggero D", "year": 2026, "journal": "Journal of Clinical Investigation", "doi": "10.1172/JCI199709", "pmid": "42454485", "pmcid": "PMC13367966", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Lymphoma cell lines / mouse", "peer_reviewed": true, "finding": "SLC15A3-mediated dipeptide import sustains mTORC1 activation in B cell lymphomas, enabling resistance to antimetabolite chemotherapy. Silencing SLC15A3 lowered mTORC1 activity and restored sensitivity to 6-mercaptopurine, and the resistant lymphomas, but not the parental tumours, were selectively sensitive to rapamycin in culture and in vivo.", "url": "https://mtor-atlas.org/study/YAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAN2026.json" }, { "sid": "GIN1999", "title": "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism", "authors": "Gingras AC; Sonenberg N et al.", "year": 1999, "journal": "Genes & development", "doi": "10.1101/gad.13.11.1422", "pmid": "10364159", "pmcid": "PMC316780", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells; in vitro", "peer_reviewed": true, "finding": "4E-BP1 is phosphorylated by an ordered, priming two-step mechanism that controls its release of eIF4E.", "url": "https://mtor-atlas.org/study/GIN1999/", "api_url": "https://mtor-atlas.org/api/v1/studies/GIN1999.json" }, { "sid": "BEN2016", "title": "mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle", "authors": "Ben-Sahra I; Manning BD et al.", "year": 2016, "journal": "Science", "doi": "10.1126/science.aad0489", "pmid": "26912861", "pmcid": "PMC4786372", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1 promotes purine synthesis via ATF4-driven mitochondrial tetrahydrofolate metabolism.", "url": "https://mtor-atlas.org/study/BEN2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/BEN2016.json" }, { "sid": "DUR2026", "title": "Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution", "authors": "Duran-Ortiz S; List EO; Ikeno Y; Benayoun BA; Berryman DE; Kopchick JJ et al.", "year": 2026, "journal": "Aging cell", "doi": "10.1111/acel.70695", "pmid": "42698366", "pmcid": "PMC13545643", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Tamoxifen-inducible whole-body Ghr knockout mice induced at 12 months of age (12mGHRKO), both sexes; liver single-nucleus RNA-seq", "peer_reviewed": true, "finding": "Deleting the growth hormone receptor in mice at 12 months of age, in middle age and long after development is complete, still significantly extended lifespan in both sexes without major effects on body growth. Males showed improved insulin sensitivity and were protected against age-related decline in neuromuscular performance and bone microarchitecture despite increased adiposity. Liver snRNA-seq revealed sex-dimorphic remodelling, including a shift toward feminised gene expression in male hepatocytes consistent with loss of pulsatile GH-STAT5 signalling. Important because most GH/IGF-1 longevity models are congenital: this shows a midlife start is still sufficient, which matters for translating growth-signalling (and by extension mTOR-adjacent) interventions to adults.", "url": "https://mtor-atlas.org/study/DUR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DUR2026.json" }, { "sid": "LV2026S", "title": "Deubiquitinase USP7 stabilizes the histone demethylase KDM5B and promotes the progression of renal fibrosis through the TSC1/mTOR axis", "authors": "Lv S; Zhang Xiaoyan et al.", "year": 2026, "journal": "Molecular biomedicine", "doi": "10.1186/s43556-026-00531-3", "pmid": "42554966", "pmcid": "PMC13442801", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse (UUO and unilateral renal ischemia-reperfusion injury models); human CKD kidney tissue (correlative)", "peer_reviewed": true, "finding": "USP7 deubiquitinates and stabilizes the histone demethylase KDM5B, which represses TSC1 transcription and thereby activates mTOR, promoting kidney fibrosis in two mouse injury models; USP7 is upregulated in human CKD kidneys and correlates with fibrosis severity. Genetic or pharmacological USP7 inhibition restores TSC1 expression, suppresses mTOR activation, and attenuates fibrosis in these mice, making the USP7-KDM5B-TSC1-mTOR axis a candidate intervention point; the human data are correlative only.", "url": "https://mtor-atlas.org/study/LV2026S/", "api_url": "https://mtor-atlas.org/api/v1/studies/LV2026S.json" }, { "sid": "MEI2008", "title": "Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function", "authors": "Meikle L; Kwiatkowski DJ et al.", "year": 2008, "journal": "The Journal of neuroscience", "doi": "10.1523/JNEUROSCI.0955-08.2008", "pmid": "18495876", "pmcid": "PMC2633923", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (Tsc1 neuronal KO)", "peer_reviewed": true, "finding": "mTOR inhibition rescues a neuronal tuberous-sclerosis model, supporting rapamycin for TSC neurology.", "url": "https://mtor-atlas.org/study/MEI2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/MEI2008.json" }, { "sid": "DEM2026", "title": "IDH3 regulates citrate homeostasis to control metabolic fitness and venetoclax resistance of AML stem cells", "authors": "Demir A; Mönnig M; Aroua N; Besiridou E; Schmidt V; et al.; Raffel S", "year": 2026, "journal": "Blood", "doi": "10.1182/blood.2026034181", "pmid": "42752592", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human AML patient samples, bone marrow organoids, xenograft mice", "peer_reviewed": true, "finding": "IDH3A loss in AML leukemic stem cells reduces TCA cycle flux and raises intracellular citrate, activating AMPK and suppressing mTORC1 (lowering translation), which sensitizes cells to BCL2 inhibition by venetoclax - nominating the IDH3A-citrate-AMPK-mTORC1 axis as a target to overcome venetoclax/azacitidine resistance.", "url": "https://mtor-atlas.org/study/DEM2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEM2026.json" }, { "sid": "GRA2014", "title": "A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity", "authors": "Grabiner BC; Sabatini DM et al.", "year": 2014, "journal": "Cancer discovery", "doi": "10.1158/2159-8290.CD-13-0929", "pmid": "24631838", "pmcid": "PMC4012430", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cell panels", "peer_reviewed": true, "finding": "A spectrum of cancer-associated MTOR mutations are hyperactivating and predict rapamycin sensitivity.", "url": "https://mtor-atlas.org/study/GRA2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/GRA2014.json" }, { "sid": "SONH2026", "title": "Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF", "authors": "Hangyul Song, Chahyeon Yun, Yunju Choi, Wooju Jeong, Yumin Kim, Jaeyoung Kim, Ju-Yeon Lee, Dongryeol Ryu, Sang-Wook Park, Chang-Myung Oh", "year": 2026, "journal": "Experimental and Molecular Medicine", "doi": "10.1038/s12276-026-01776-2", "pmid": "42432192", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (HFpEF two-hit model)", "peer_reviewed": true, "finding": "Urolithin A ameliorates HFpEF cardiac remodeling in mice by activating AMPK and inhibiting mTOR to restore mitophagic flux, while simultaneously remodeling the gut microbiome-ceramide axis to reduce lipotoxic stress.", "url": "https://mtor-atlas.org/study/SONH2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SONH2026.json" }, { "sid": "LANDOAS2026", "title": "Does the duration of exposure to everolimus influence the occurrence of chronic lung allograft dysfunction?", "authors": "Landoas A; Perrier Q; Falque L et al.", "year": 2026, "journal": "Transplant Immunology", "doi": "10.1016/j.trim.2026.102436", "pmid": null, "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (single-centre retrospective observational)", "peer_reviewed": true, "finding": "In lung transplant recipients, later introduction of everolimus and a greater number of treatment interruptions were both risk factors for chronic lung allograft dysfunction; earlier, uninterrupted treatment was associated with lower CLAD risk (retrospective, single-centre; causality not established).", "url": "https://mtor-atlas.org/study/LANDOAS2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LANDOAS2026.json" }, { "sid": "TIW2026", "title": "Firefox, a protein encoded by circular RNA circPVT1, is essential for MYC-driven oncogenesis", "authors": "Tiwari A, Paithane U, Tashiro K, Hall B, Friedlein J, Saraswat M, Saulnier O, Barbosa K, Trinh Q, Bagchi A, et al.", "year": 2026, "journal": "Genes & Development", "doi": "10.1101/gad.353355.125", "pmid": "42618323", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human MYC-amplified cancer cell lines; xenograft mouse models", "peer_reviewed": true, "finding": "A micropeptide (Firefox/FFX) encoded by the circular RNA circPVT1 stimulates AKT-mTORC1 signaling and cap-dependent translation to sustain MYC protein abundance and transcriptional output. FFX depletion reduces MYC levels and impairs tumor growth in MYC-amplified xenograft models, identifying an mTORC1-linked vulnerability in MYC-driven cancers.", "url": "https://mtor-atlas.org/study/TIW2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/TIW2026.json" }, { "sid": "MAR2026", "title": "EVERolimus effectiveness after proGREssion on ENdocrine therapy plus CDK4/6 inhibitor for ER-positive/HER2-negative advanced breast cancer: EVERGREEN study", "authors": "Diogo Martins-Branco, Soraia Lobo-Martins, Philippe Aftimos, Bernardo Pereira, Leonor Vasconcelos de Matos, Leonor Fernandes, Guilherme Nader-Marta, Michel Moreau, Donatienne Taylor, Francois P Duhoux, Evandro de Azambuja", "year": 2026, "journal": "Breast Cancer Research and Treatment", "doi": "10.1007/s10549-026-08012-5", "pmid": "42429895", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (multicenter retrospective cohort)", "peer_reviewed": true, "finding": "Everolimus added to endocrine therapy provided modest but statistically significant PFS benefit (5.0 vs 4.3 months; HR 0.68) in ER+/HER2- advanced breast cancer post-CDK4/6 inhibitor progression, without demonstrable OS benefit, supporting selective use. Retrospective and non-randomised, so treatment-selection bias cannot be excluded.", "url": "https://mtor-atlas.org/study/MAR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MAR2026.json" }, { "sid": "AYL2015", "title": "Architecture of human mTOR complex 1", "authors": "Aylett CH; Maier T et al.", "year": 2015, "journal": "Science", "doi": "10.1126/science.aaa3870", "pmid": "26678875", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM architecture of human mTORC1 reveals its dimeric organization and active site access.", "url": "https://mtor-atlas.org/study/AYL2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/AYL2015.json" }, { "sid": "LASSILA2026", "title": "Pregnane X receptor-mediated liver growth: a controlled clinical trial in healthy volunteers and identification of the role of AKT-MTOR pathway in mouse.", "authors": "Lassila P; Karpale M; Kummu O et al.", "year": 2026, "journal": "Archives of Toxicology", "doi": "10.1007/s00204-026-04526-5", "pmid": null, "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human controlled clinical trial (n=16); mouse (PXR-humanised, PCN)", "peer_reviewed": true, "finding": "One week of rifampicin increased the liver volume-to-body-weight ratio by 2.7% in 16 healthy volunteers, and PXR activation enlarged the liver in male mice, accompanied by increased AKT-MTOR pathway activity, without YAP activation.", "url": "https://mtor-atlas.org/study/LASSILA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LASSILA2026.json" }, { "sid": "BAN2014", "title": "Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls", "authors": "Bannister CA et al.", "year": 2014, "journal": "Diabetes, Obesity and Metabolism", "doi": "10.1111/dom.12354", "pmid": "25041462", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, retrospective cohort (n=180,926)", "peer_reviewed": true, "finding": "Diabetic patients started on metformin had longer median survival than matched non-diabetic controls without the drug. Retrospective and observational: consistent with a survival benefit, but confounding by indication and healthy-adherer effects cannot be excluded.", "url": "https://mtor-atlas.org/study/BAN2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAN2014.json" }, { "sid": "KAR2017", "title": "Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2", "authors": "Karuppasamy M; Schaffitzel C et al.", "year": 2017, "journal": "Nature communications", "doi": "10.1038/s41467-017-01862-0", "pmid": "29170376", "pmcid": "PMC5700991", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM structure of yeast TORC2 reveals its overall architecture and rapamycin insensitivity.", "url": "https://mtor-atlas.org/study/KAR2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/KAR2017.json" }, { "sid": "BAB2025", "title": "Restriction of individual branched-chain amino acids has distinct effects on the development and progression of Alzheimer's disease in 3xTg mice", "authors": "Babygirija R; Lamming DW et al.", "year": 2026, "journal": "Advanced Science", "doi": "10.1002/advs.202515220", "pmid": "41817439", "pmcid": "PMC13248761", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (Alzheimer's disease model)", "peer_reviewed": true, "finding": "UPDATE (was bioRxiv preprint at seed time, peer-reviewed and published in Advanced Science March 2026). Restricting individual branched-chain amino acids has distinct, sex-specific effects on cognition and AD pathology in 3xTg mice; restriction of isoleucine and valine (but not leucine) promotes metabolic health. Note: the different BCAAs act differentially on mTORC1, which is why single-amino-acid restriction matters.", "url": "https://mtor-atlas.org/study/BAB2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/BAB2025.json" }, { "sid": "CHE2008", "title": "TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species", "authors": "Chen C; Liu Yu; Liu R; Ikenoue T; Guan KL; Liu Yang; Zheng P", "year": 2008, "journal": "Journal of Experimental Medicine", "doi": "10.1084/jem.20081297", "pmid": "18809716", "pmcid": "PMC2556783", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (conditional Tsc1 knockout)", "peer_reviewed": true, "finding": "Showed why blood stem cells must keep mTOR LOW. Deleting TSC1 (which unleashes mTOR) drove resting stem cells into rapid division, flooded them with reactive oxygen species, and burned out their ability to self-renew. An antioxidant rescued them. A key link between mTOR, stem-cell exhaustion, and tissue aging.", "url": "https://mtor-atlas.org/study/CHE2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHE2008.json" }, { "sid": "DEM2014", "title": "Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2", "authors": "Demetriades C; Teleman AA et al.", "year": 2014, "journal": "Cell", "doi": "10.1016/j.cell.2014.01.024", "pmid": "24529380", "pmcid": "PMC4346203", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Amino-acid starvation recruits TSC2 to the lysosome to inhibit Rheb and TORC1.", "url": "https://mtor-atlas.org/study/DEM2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEM2014.json" }, { "sid": "PEREZ2026", "title": "A cross-species drug-discovery platform to accelerate the identification of lifespan-extending interventions", "authors": "Perez K; Schoenfeldt L; Phelps GB; Parras A; Morin J; Pinto C; Guilmot S; Oliveira T; Silveira M; Dolfi L; Ocampo A", "year": 2026, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2026.117897", "pmid": "42671914", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Five model organisms: S. cerevisiae, C. elegans, D. melanogaster, killifish, mice", "peer_reviewed": true, "finding": "An integrated high-throughput lifespan-screening platform spanning yeast, nematodes, flies, killifish and mice, evaluating >400 compounds across thousands of conditions using automated imaging and deep-learning death detection. Cross-species integration identifies geroprotectors active in multiple species and shows convergence on known and novel conserved longevity pathways. Methodological infrastructure for the question the Atlas keeps running into: which single-species lifespan results actually generalise. Note the abstract does not name individual hit compounds, so the specific standing of rapamycin/mTOR in this screen cannot be read off the abstract alone.", "url": "https://mtor-atlas.org/study/PEREZ2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/PEREZ2026.json" }, { "sid": "SAN2010", "title": "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids", "authors": "Sancak Y; Bar-Peled L; Zoncu R; Markhard AL; Nada S; Sabatini DM", "year": 2010, "journal": "Cell", "doi": "10.1016/j.cell.2010.02.024", "pmid": "20381137", "pmcid": "PMC3024592", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + Drosophila", "peer_reviewed": true, "finding": "Established WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb lives. Amino acids work by controlling this translocation.", "url": "https://mtor-atlas.org/study/SAN2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAN2010.json" }, { "sid": "ZON2011", "title": "mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase", "authors": "Zoncu R; Bar-Peled L; Efeyan A; Wang S; Sancak Y; Sabatini DM", "year": 2011, "journal": "Science", "doi": "10.1126/science.1207056", "pmid": "22053050", "pmcid": "PMC3211112", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells + cell-free reconstitution", "peer_reviewed": true, "finding": "Showed amino acid sensing starts INSIDE the lysosome: amino acids accumulate in the lumen and the v-ATPase relays that signal outward ('inside-out') to Ragulator-Rag. A surprising twist on where the cell measures its nutrient status.", "url": "https://mtor-atlas.org/study/ZON2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZON2011.json" }, { "sid": "ZHANG2026C", "title": "Anti-breast cancer effects of the Xingxiao Pill are associated with inhibition of the ErbB3/PI3K/AKT/mTOR pathway, modulation of amino acid metabolism, and promotion of apoptosis.", "authors": "Zhang Jingyue; Cheng J; Cao F et al.", "year": 2026, "journal": "Journal of Ethnopharmacology", "doi": "10.1016/j.jep.2026.122321", "pmid": "42648410", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (4T1 subcutaneous model); breast cancer cell lines", "peer_reviewed": true, "finding": "Xingxiao Pill inhibited 4T1 breast cancer growth in vitro and in vivo by suppressing ErbB3/PI3K/AKT/mTOR signalling and reshaping amino acid metabolism; cinnamic acid and palmitic acid were identified as constituents that bind mTOR.", "url": "https://mtor-atlas.org/study/ZHANG2026C/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHANG2026C.json" }, { "sid": "ROG2019", "title": "Structural basis for the docking of mTORC1 on the lysosomal surface", "authors": "Rogala KB; Sabatini DM et al.", "year": 2019, "journal": "Science", "doi": "10.1126/science.aay0166", "pmid": "31601708", "pmcid": "PMC7176403", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure (human proteins, cell-free reconstitution) + cell-based mutagenesis", "peer_reviewed": true, "finding": "3.2-angstrom cryo-EM structure of Raptor bound to Rag-Ragulator, showing how Raptor reads out the nutrient-dependent nucleotide state of the Rag GTPases: one part of Raptor senses RagA's nucleotide state, a separate 'claw' senses RagC's, and both have to be in the correct nutrient-signalling combination before Raptor is allowed to dock. Mutating the contact points blocks mTORC1 from reaching the lysosome and inhibits its signalling, which is the functional evidence behind the structural claim. Combined with a separate structure of mTORC1 bound to its activator Rheb, the paper builds a model of the complete, active mTORC1 sitting on the lysosome. Boundary: cryo-EM of a complex reconstituted from purified human proteins, not a live-cell measurement.", "url": "https://mtor-atlas.org/study/ROG2019/", "api_url": "https://mtor-atlas.org/api/v1/studies/ROG2019.json" }, { "sid": "WOLF2017", "title": "The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway", "authors": "Wolfson RL; Sabatini DM et al.", "year": 2017, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2017.07.001", "pmid": "28768171", "pmcid": "PMC5560103", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of the newly discovered amino-acid sensors feeding into mTORC1.", "url": "https://mtor-atlas.org/study/WOLF2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/WOLF2017.json" }, { "sid": "LIX2010", "title": "mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists", "authors": "Li N; Duman RS et al.", "year": 2010, "journal": "Science", "doi": "10.1126/science.1190287", "pmid": "20724638", "pmcid": "PMC3116441", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat", "peer_reviewed": true, "finding": "Ketamine's rapid antidepressant action requires mTOR-dependent synaptogenesis in prefrontal cortex.", "url": "https://mtor-atlas.org/study/LIX2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIX2010.json" }, { "sid": "POW2011", "title": "Regulation of immune responses by mTOR", "authors": "Powell JD; Horton MR et al.", "year": 2011, "journal": "Annual review of immunology", "doi": "10.1146/annurev-immunol-020711-075024", "pmid": "22136167", "pmcid": "PMC3616892", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review of mTOR as an integrator of immune-cell metabolism and differentiation.", "url": "https://mtor-atlas.org/study/POW2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/POW2011.json" }, { "sid": "ZIN2011", "title": "Activation of mTORC2 by association with the ribosome", "authors": "Zinzalla V; Hall MN et al.", "year": 2011, "journal": "Cell", "doi": "10.1016/j.cell.2011.02.014", "pmid": "21376236", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC2 is activated by direct association with the ribosome downstream of PI3K.", "url": "https://mtor-atlas.org/study/ZIN2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZIN2011.json" }, { "sid": "TAN2026", "title": "SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer", "authors": "Tang B; Sun R; Shao J; Wu QY; Yan Y; Wang D; Yu Z; Hu L; Chen Y; Liao C; Wei Q; Bao Y; Huang H", "year": 2026, "journal": "Nature Communications", "doi": "10.1038/s41467-026-77043-9", "pmid": "42778578", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "ccRCC cell lines (in vitro); mouse xenograft tumors treated with a NEK7-targeting PROTAC", "peer_reviewed": true, "finding": "Identifies a mechanism of mTOR-inhibitor (everolimus/temsirolimus) resistance in clear cell renal cell carcinoma: SPOP-driven K63-linked ubiquitination of ZMYND8 excludes it from phase-separation compartments, enabling a ZMYND8-ZHX2 complex that drives NEK7 transcription and alternative p70S6K activation independent of mTOR inhibition. A NEK7-targeting PROTAC restored everolimus sensitivity in ccRCC cells and mouse tumors, nominating NEK7 as a target to overcome mTOR-inhibitor resistance.", "url": "https://mtor-atlas.org/study/TAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/TAN2026.json" }, { "sid": "PEN2017", "title": "SZT2 dictates GATOR control of mTORC1 signalling", "authors": "Peng M; Li MO et al.", "year": 2017, "journal": "Nature", "doi": "10.1038/nature21378", "pmid": "28199315", "pmcid": "PMC5570594", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SZT2 organizes GATOR1/GATOR2 to dictate amino-acid control of mTORC1.", "url": "https://mtor-atlas.org/study/PEN2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/PEN2017.json" }, { "sid": "NIC2023", "title": "Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor", "authors": "Nicastro R; Brohée L; Alba J; Nüchel J; Figlia G; Kipschull S; Gollwitzer P; Romero-Pozuelo J; Fernandes SA; Lamprakis A; Vanni S; Teleman AA; De Virgilio C; Demetriades C", "year": 2023, "journal": "Nature Cell Biology", "doi": "10.1038/s41556-023-01198-6", "pmid": "37563253", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast and mammalian cells", "peer_reviewed": true, "finding": "Malonyl-CoA, an intermediate of fatty-acid biosynthesis, binds the mTOR catalytic pocket directly and acts as a conserved ATP-competitive inhibitor of mTORC1; when fatty acid synthase is downregulated, rising malonyl-CoA feeds back to dampen mTORC1 activity, linking lipogenic capacity to overall biosynthetic output.", "url": "https://mtor-atlas.org/study/NIC2023/", "api_url": "https://mtor-atlas.org/api/v1/studies/NIC2023.json" }, { "sid": "SHA2004", "title": "Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies", "authors": "Shah OJ; Wang Zhiyong; Hunter T", "year": 2004, "journal": "Current Biology", "doi": "10.1016/j.cub.2004.08.026", "pmid": "15380067", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "The companion paper to Harrington 2004, published two months later. In cultured mammalian cells, constitutive Rheb/mTOR/S6K activity depletes IRS1 and IRS2, producing cellular insulin resistance and impaired survival signalling. Together the two papers establish the S6K1 -> IRS negative feedback arm.", "url": "https://mtor-atlas.org/study/SHA2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHA2004.json" }, { "sid": "TAN2024", "title": "Targeting mTOR restores tau-induced metabolic, mitochondrial, and cognitive deficits in a tauopathy mouse model", "authors": "Tang Z; Guo M; Ding Y; Wen Y; Li B; Xiao Y; Ni R; Guan Z; Qi XL", "year": 2024, "journal": "bioRxiv (preprint)", "doi": "10.1101/2024.11.24.625068", "pmid": null, "pmcid": null, "evidence": { "code": "PP", "label": "Preprint, not peer-reviewed", "note": "this describes the kind of study, not its quality" }, "category": "Preprint", "model_system": "Mouse (Tau3E-overexpressing, hippocampal CA3)", "peer_reviewed": false, "finding": "In mice engineered to overexpress a phosphomimetic tau variant, one week of rapamycin partially mitigated tau-driven mitochondrial dysfunction and cognitive impairment in the Morris water maze - extends the mTOR-autophagy-neurodegeneration link (already seen with Huntington's) to a direct tau-phosphorylation mechanism relevant to Alzheimer's.", "url": "https://mtor-atlas.org/study/TAN2024/", "api_url": "https://mtor-atlas.org/api/v1/studies/TAN2024.json" }, { "sid": "HUD2007", "title": "Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma", "authors": "Hudes G et al.", "year": 2007, "journal": "New England Journal of Medicine", "doi": "10.1056/NEJMoa066838", "pmid": "17538086", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase III RCT (n=626)", "peer_reviewed": true, "finding": "Temsirolimus alone extended median overall survival to 10.9 months versus 7.3 months with interferon alfa in poor-prognosis metastatic kidney cancer; rash, hyperglycemia, and hyperlipidemia were more common with temsirolimus.", "url": "https://mtor-atlas.org/study/HUD2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/HUD2007.json" }, { "sid": "CAR2017", "title": "Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing", "authors": "Carroll B; Nelson G; Rabanal-Ruiz Y; Kucheryavenko O; Dunhill-Turner NA; Chesterman CC; Zahari Q; Zhang T; Conduit SE; Mitchell CA; Maddocks ODK; Lovat P; von Zglinicki T; Korolchuk VI", "year": 2017, "journal": "The Journal of cell biology", "doi": "10.1083/jcb.201610113", "pmid": "28566325", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human fibroblasts made senescent by stress, replicative exhaustion or oncogene activation", "peer_reviewed": true, "finding": "Explains why mTORC1 stays switched on in senescent cells. In human fibroblasts rendered senescent three different ways, mTORC1 is constitutively active and no longer responds to serum or amino acid withdrawal. The defect is upstream, not in mTORC1 itself: it is driven in part by depolarisation of the senescent plasma membrane, which leads to primary cilia defects and a failure to shut off growth-factor signalling, while increased autophagy and high intracellular amino acid levels may act to support the nutrient arm. Correcting these inputs restored sensitivity of the pathway and killed the cells, which frames persistent mTORC1 signalling as a survival dependency of senescent cells rather than a by-product of senescence.", "url": "https://mtor-atlas.org/study/CAR2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/CAR2017.json" }, { "sid": "THO2012", "title": "A unifying model for mTORC1-mediated regulation of mRNA translation", "authors": "Thoreen CC; Chantranupong L; Keys HR; Wang T; Gray NS; Sabatini DM", "year": 2012, "journal": "Nature", "doi": "10.1038/nature11083", "pmid": "22552098", "pmcid": "PMC3347774", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse cells (ribosome profiling)", "peer_reviewed": true, "finding": "Used ribosome profiling with the complete inhibitor Torin1 to address a long-standing debate: in these cells, mTORC1's translational control runs largely through the 4E-BP family acting on a specific class of mRNAs (TOP motifs). Losing just the 4E-BPs makes translation of TOP mRNAs resistant to mTOR inhibition - naming them the master effectors.", "url": "https://mtor-atlas.org/study/THO2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/THO2012.json" }, { "sid": "WUL2006", "title": "TOR signaling in growth and metabolism", "authors": "Wullschleger S; Hall MN et al.", "year": 2006, "journal": "Cell", "doi": "10.1016/j.cell.2006.01.016", "pmid": "16469695", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Landmark review synthesizing TOR signalling in growth and metabolism across organisms.", "url": "https://mtor-atlas.org/study/WUL2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/WUL2006.json" }, { "sid": "URF2017", "title": "A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs", "authors": "Urfer SR; Kaeberlein M et al.", "year": 2017, "journal": "GeroScience", "doi": "10.1007/s11357-017-9972-z", "pmid": "28374166", "pmcid": "PMC5411365", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Companion dogs (client-owned, RCT)", "peer_reviewed": true, "finding": "A short 10-week course of low-dose rapamycin in healthy pet dogs caused no clinical side effects, and echocardiography suggested improved measures of heart function.", "url": "https://mtor-atlas.org/study/URF2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/URF2017.json" }, { "sid": "JUN2015", "title": "Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9", "authors": "Jung J; Behrends C et al.", "year": 2015, "journal": "Molecular and cellular biology", "doi": "10.1128/MCB.00125-15", "pmid": "25963655", "pmcid": "PMC4475919", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SLC38A9, a lysosomal membrane protein, mediates amino-acid-dependent mTORC1 activation.", "url": "https://mtor-atlas.org/study/JUN2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/JUN2015.json" }, { "sid": "HOW2017", "title": "Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex", "authors": "Howell JJ; Hellberg K; Turner M; Talbott G; Kolar MJ; Ross DS; Hoxhaj G; Saghatelian A; Shaw RJ; Manning BD", "year": 2017, "journal": "Cell Metabolism", "doi": "10.1016/j.cmet.2016.12.009", "pmid": "28089566", "pmcid": "PMC5299044", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse liver + primary hepatocytes", "peer_reviewed": true, "finding": "Pinned down HOW the diabetes drug metformin - a major longevity candidate - actually reaches mTOR. In the liver, metformin lowers cellular energy, and at low doses this shuts down mTORC1 specifically through AMPK and the TSC complex. Direct mechanistic bridge between a widely-used drug, energy sensing, and the mTOR pathway.", "url": "https://mtor-atlas.org/study/HOW2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/HOW2017.json" }, { "sid": "GOL2022", "title": "A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids", "authors": "Gollwitzer P; Grützmacher N; Wilhelm S; Kümmel D; Demetriades C", "year": 2022, "journal": "Nature Cell Biology", "doi": "10.1038/s41556-022-00976-y", "pmid": "36097072", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (genetically modified Rag-paralogue cell lines)", "peer_reviewed": true, "finding": "The four mammalian Rag GTPase paralogues are not functionally interchangeable: RagC/D determines substrate specificity (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding), while RagA/B determines the response to amino acid withdrawal (RagB-expressing cells keep mTORC1 lysosomal and active even upon starvation). Author correction issued 2023 (PMID 36536178, no change to conclusions).", "url": "https://mtor-atlas.org/study/GOL2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/GOL2022.json" }, { "sid": "HAN2025", "title": "What is the clinical evidence to support off-label rapamycin therapy in healthy adults?", "authors": "Hands JM; Lustgarten MS; Frame LA; Rosen B", "year": 2025, "journal": "Aging (Albany NY)", "doi": "10.18632/aging.206300", "pmid": "40778880", "pmcid": "PMC12422820", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Narrative review + PhenoAge modeling of one cohort", "peer_reviewed": true, "finding": "A deliberately cautious review of low-dose rapamycin in healthy adults, and re-models one cohort using the PhenoAge biological-aging clock. Verdict: despite strong animal lifespan data, human evidence does NOT yet prove rapamycin delays aging in healthy people. A valuable counterweight to longevity-community hype - it holds the human evidence to a strict standard rather than over-reading promising signals.", "url": "https://mtor-atlas.org/study/HAN2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAN2025.json" }, { "sid": "BRO1994", "title": "A mammalian protein targeted by G1-arresting rapamycin-receptor complex", "authors": "Brown EJ; Schreiber SL et al.", "year": 1994, "journal": "Nature", "doi": "10.1038/369756a0", "pmid": "8008069", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Bovine brain; in vitro", "peer_reviewed": true, "finding": "Purified FRAP (mTOR) as the mammalian FKBP12-rapamycin target homologous to yeast TOR1/2.", "url": "https://mtor-atlas.org/study/BRO1994/", "api_url": "https://mtor-atlas.org/api/v1/studies/BRO1994.json" }, { "sid": "DAL2016", "title": "A systems study reveals concurrent activation of AMPK and mTOR by amino acids", "authors": "Dalle Pezze P; Ruf S; Sonntag AG; Langelaar-Makkinje M; Hall P; Heberle AM; Razquin Navas P; van Eunen K; Tölle RC; Schwarz JJ; Wiese H; Warscheid B; Deitersen J; Stork B; Fäßler E; Schäuble S; Hahn U; Horvatovich P; Shanley DP; Thedieck K", "year": 2016, "journal": "Nature Communications", "doi": "10.1038/ncomms13254", "pmid": "27869123", "pmcid": "PMC5121333", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines; amino acid re-addition time courses, quantitative proteomics and dynamic modelling", "peer_reviewed": true, "finding": "Adding amino acids back to starved cells switched on AMPK, PI3K and mTORC2 acutely and independently of mTORC1, at the same time as mTOR. AMPK activation ran through CaMKK-beta and, under amino acid sufficiency, AMPK kept autophagy going via ULK1. So the textbook picture of AMPK and mTORC1 as simple opposites does not hold in the first minutes after feeding - which matters for how the AMPK-ULK1 feedback arm behaves over time.", "url": "https://mtor-atlas.org/study/DAL2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/DAL2016.json" }, { "sid": "SHE2018", "title": "Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes", "authors": "Shen K; Sabatini DM et al.", "year": 2018, "journal": "Nature", "doi": "10.1038/nature26158", "pmid": "29590090", "pmcid": "PMC5975964", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Cryo-EM structures of GATOR1 and GATOR1-Rag complexes reveal GAP and inhibitory-clamp mechanisms.", "url": "https://mtor-atlas.org/study/SHE2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/SHE2018.json" }, { "sid": "FIN2002", "title": "Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E", "authors": "Fingar DC; Blenis J et al.", "year": 2002, "journal": "Genes & development", "doi": "10.1101/gad.995802", "pmid": "12080086", "pmcid": "PMC186342", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTOR controls mammalian cell size through its downstream translational targets S6K1 and 4E-BP1/eIF4E.", "url": "https://mtor-atlas.org/study/FIN2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/FIN2002.json" }, { "sid": "ALS2026", "title": "Disruption of the insulin/IGF-1 signaling pathway in Caenorhabditis elegans dramatically increases male longevity and enhances reproductive health late in life", "authors": "Al-Saadi RS; Lewack HB; Phillips PC", "year": 2026, "journal": "Aging (Albany NY)", "doi": "10.18632/aging.206411", "pmid": "42641111", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "C. elegans (males; auxin-inducible degron degradation of DAF-2/IGF-1 receptor)", "peer_reviewed": true, "finding": "Ubiquitous auxin-inducible degradation of the DAF-2/IGF-1 receptor in C. elegans males increases median lifespan by more than 440% — among the largest lifespan extensions reported for a single intervention — and prolongs male reproductive function late in life. Notably, degrading DAF-2 specifically in the male germline shortened lifespan, the opposite of its effect in hermaphrodites, underlining that pro-longevity nutrient-sensing interventions can act in a sex- and tissue-dependent way.", "url": "https://mtor-atlas.org/study/ALS2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ALS2026.json" }, { "sid": "GUIB2026", "title": "Maternal Sirolimus Therapy for Fetal Extensive Lymphatic Cystic Malformation: Selection Criteria, Management, and Outcomes in a Series of Six Cases", "authors": "Guibaud L; Bordas-Fournel M; Cabet S; Le Vaillant C; Bruel A; Lefran‡ois T; Megier C; Benachi A; Sohier M; Gallois Y; Somon T; Jouannic J-M; Canaud G; Guilhem A; Atallah A; Fraissenon A", "year": 2026, "journal": "Prenatal Diagnosis", "doi": "10.1002/pd.70230", "pmid": "42607031", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": null, "peer_reviewed": true, "finding": "Maternal rapamycin (sirolimus) therapy for extensive fetal lymphatic malformations. Prenatal mTOR inhibition feasible with partial/marked lesion regression in 5/6 newborns; transplacental transfer observed. Observational case series (n=6); confounding by indication not excluded.", "url": "https://mtor-atlas.org/study/GUIB2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/GUIB2026.json" }, { "sid": "KIM2002", "title": "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery", "authors": "Kim DH; Sarbassov DD; Ali SM; King JE; Latek RR; Erdjument-Bromage H; Tempst P; Sabatini DM", "year": 2002, "journal": "Cell", "doi": "10.1016/s0092-8674(02)00808-5", "pmid": "12150925", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human/rodent cell lines (biochemistry)", "peer_reviewed": true, "finding": "Discovery of Raptor as the defining partner of mTOR in mTORC1. This is the paper that gives mTORC1 its identity: Raptor is the scaffold that lets mTOR find and phosphorylate its targets (S6K1), and the complex is stabilized under starvation. Companion paper to Hara 2002.", "url": "https://mtor-atlas.org/study/KIM2002/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2002.json" }, { "sid": "CHO1996", "title": "Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP", "authors": "Choi J; Chen J; Schreiber SL; Clardy J", "year": 1996, "journal": "Science", "doi": "10.1126/science.273.5272.239", "pmid": "8662507", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "X-ray crystallography (structural biology)", "peer_reviewed": true, "finding": "The crystal structure that showed HOW rapamycin works at the atomic level: one rapamycin molecule glues two proteins together - FKBP12 and mTOR's FRB domain - by plugging into two hydrophobic pockets at once. A textbook example of a small molecule acting as 'molecular glue' to force protein dimerization.", "url": "https://mtor-atlas.org/study/CHO1996/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHO1996.json" }, { "sid": "ZON2010", "title": "mTOR: from growth signal integration to cancer, diabetes and ageing", "authors": "Zoncu R; Sabatini DM et al.", "year": 2010, "journal": "Nature reviews. Molecular cell biology", "doi": "10.1038/nrm3025", "pmid": "21157483", "pmcid": "PMC3390257", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Authoritative review of mTOR from growth-signal integration to disease.", "url": "https://mtor-atlas.org/study/ZON2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZON2010.json" }, { "sid": "PET2011", "title": "mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway", "authors": "Peterson TR; Sabatini DM et al.", "year": 2011, "journal": "Cell", "doi": "10.1016/j.cell.2011.06.034", "pmid": "21816276", "pmcid": "PMC3336367", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1 controls lipin-1 nuclear localization to regulate SREBP and lipid synthesis.", "url": "https://mtor-atlas.org/study/PET2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/PET2011.json" }, { "sid": "DEL2009", "title": "The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment", "authors": "Delgoffe GM; Powell JD et al.", "year": 2009, "journal": "Immunity", "doi": "10.1016/j.immuni.2009.04.014", "pmid": "19538929", "pmcid": "PMC2768135", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse (T cells)", "peer_reviewed": true, "finding": "T cells lacking mTOR fail to become normal effector cells and default toward regulatory T cells, showing mTOR is a master switch for immune cell fate.", "url": "https://mtor-atlas.org/study/DEL2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEL2009.json" }, { "sid": "CHR2009", "title": "AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity", "authors": "Chresta CM; Pass M et al.", "year": 2009, "journal": "Cancer research", "doi": "10.1158/0008-5472.CAN-09-1751", "pmid": "20028854", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cancer cells; xenograft", "peer_reviewed": true, "finding": "AZD8055, an ATP-competitive mTOR kinase inhibitor, blocks both mTORC1 and mTORC2 (rapamycin-resistant outputs).", "url": "https://mtor-atlas.org/study/CHR2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHR2009.json" }, { "sid": "GAR2008", "title": "mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)", "authors": "Garcia-Martinez JM; Alessi DR et al.", "year": 2008, "journal": "The Biochemical journal", "doi": "10.1042/BJ20081668", "pmid": "18925875", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC2 controls hydrophobic-motif phosphorylation and activity of SGK1 in addition to Akt.", "url": "https://mtor-atlas.org/study/GAR2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAR2008.json" }, { "sid": "PYO2013", "title": "Overexpression of Atg5 in mice activates autophagy and extends lifespan", "authors": "Pyo JO; Jung YK et al.", "year": 2013, "journal": "Nature Communications", "doi": "10.1038/ncomms3300", "pmid": "23939249", "pmcid": "PMC3753544", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (Atg5-overexpressing transgenic)", "peer_reviewed": true, "finding": "Mice engineered with extra copies of the autophagy gene Atg5 lived 17% longer and were leaner and more insulin-sensitive.", "url": "https://mtor-atlas.org/study/PYO2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/PYO2013.json" }, { "sid": "NOB2005", "title": "Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase", "authors": "Nobukuni T; Joaquin M; Roccio M; Dann SG; Kim SY; Gulati P; Byfield MP; Backer JM; Natt F; Bos JL; Zwartkruis FJ; Thomas G", "year": 2005, "journal": "Proc Natl Acad Sci U S A", "doi": "10.1073/pnas.0506925102", "pmid": "16176982", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines", "peer_reviewed": true, "finding": "The companion paper to BYF2005, from a different laboratory: the amino acid input to mTORC1 is separate from the insulin input and runs through class 3 PI3K (hVps34), not through class 1 PI3K. Historically important because it states that the amino acid branch is the older one and that insulin signalling was grafted onto it. Boundary: cell lines, pharmacological and knockdown evidence; the later Rag/Ragulator account describes a different route to the same target and the two have never been fully reconciled.", "url": "https://mtor-atlas.org/study/NOB2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/NOB2005.json" }, { "sid": "ABU2017", "title": "Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes", "authors": "Abu-Remaileh M; Wyant GA; Kim C; Laqtom NN; Abbasi M; Chan SH; Freinkman E; Sabatini DM", "year": 2017, "journal": "Science", "doi": "10.1126/science.aan6298", "pmid": "29074583", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (HEK293)", "peer_reviewed": true, "finding": "Turns the lysosome from a place where mTORC1 is switched on into something mTORC1 also controls: inhibiting mTOR strongly reduces the efflux of most essential amino acids out of the lysosome, so the organelle becomes a store rather than a source. Measured directly by rapidly isolating lysosomes and profiling their contents, which is why the claim is about concentrations inside the organelle and not inferred from signalling readouts. Boundary: one human cell line, acute pharmacological inhibition.", "url": "https://mtor-atlas.org/study/ABU2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/ABU2017.json" }, { "sid": "MEL2003", "title": "Autophagy genes are essential for dauer development and life-span extension in C. elegans", "authors": "Melendez A; Levine B et al.", "year": 2003, "journal": "Science", "doi": "10.1126/science.1087782", "pmid": "12958363", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Caenorhabditis elegans", "peer_reviewed": true, "finding": "Worms lacking the autophagy gene bec-1 lost the lifespan-extending benefit of reduced insulin-like signaling - autophagy is mechanistically required for daf-2 (insulin-signalling) lifespan extension and for dauer formation in C. elegans.", "url": "https://mtor-atlas.org/study/MEL2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/MEL2003.json" }, { "sid": "PRI1992", "title": "Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase", "authors": "Price DJ; Bierer BE et al.", "year": 1992, "journal": "Science", "doi": "10.1126/science.1380182", "pmid": "1380182", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells; in vitro", "peer_reviewed": true, "finding": "Rapamycin induces dephosphorylation/inactivation of the 70 kDa S6 kinase, defining an early readout of TOR signalling.", "url": "https://mtor-atlas.org/study/PRI1992/", "api_url": "https://mtor-atlas.org/api/v1/studies/PRI1992.json" }, { "sid": "MEN2014", "title": "Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome", "authors": "Menon S; Manning BD et al.", "year": 2014, "journal": "Cell", "doi": "10.1016/j.cell.2013.11.049", "pmid": "24529379", "pmcid": "PMC4030681", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Spatial control of the TSC complex integrates insulin and nutrient inputs at the lysosome.", "url": "https://mtor-atlas.org/study/MEN2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/MEN2014.json" }, { "sid": "SEN2010", "title": "mTORC1 controls fasting-induced ketogenesis and its modulation by ageing", "authors": "Sengupta S; Sabatini DM et al.", "year": 2010, "journal": "Nature", "doi": "10.1038/nature09584", "pmid": "21179166", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse/cells", "peer_reviewed": true, "finding": "mTORC1 controls fasting-induced hepatic ketogenesis via PPARalpha, and this is blunted with age.", "url": "https://mtor-atlas.org/study/SEN2010/", "api_url": "https://mtor-atlas.org/api/v1/studies/SEN2010.json" }, { "sid": "VAN2007", "title": "Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40", "authors": "Vander Haar E; Kim DH et al.", "year": 2007, "journal": "Nature cell biology", "doi": "10.1038/ncb1547", "pmid": "17277771", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Insulin signals to mTORC1 through Akt phosphorylation of the inhibitor PRAS40.", "url": "https://mtor-atlas.org/study/VAN2007/", "api_url": "https://mtor-atlas.org/api/v1/studies/VAN2007.json" }, { "sid": "FAN2026", "title": "mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency", "authors": "Fan W; Liu H; Yang L; Sinha N; Catipovic M; Dong D; Easawaran H; Green R; Laiho M", "year": 2026, "journal": "Genes & Development", "doi": "10.1101/gad.353708.126", "pmid": "42575690", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cancer cell lines (functional genomics/CRISPR screens)", "peer_reviewed": true, "finding": "mTORC1 inhibition does not restore ribosome biogenesis but redistributes limited ribosomes away from highly-translated 5'TOP mRNAs toward survival-essential transcripts, defining a 'translational fitness' mechanism that lets cancer cells survive ribosome biogenesis deficiency.", "url": "https://mtor-atlas.org/study/FAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/FAN2026.json" }, { "sid": "GIN2026", "title": "Inferring feedback regulation from static snapshots of a single signal", "authors": "Ginzberg M; Tan C; Patel N; Kafri R", "year": 2026, "journal": "Biochemistry and Biophysics Reports", "doi": "10.1016/j.bbrep.2026.102747", "pmid": "42643853", "pmcid": "PMC13505498", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human/mammalian cultured cells (fixed-cell single-cell imaging, ergodic rate analysis)", "peer_reviewed": true, "finding": "Introduces AoF (Assay of Feedback), a perturbation-free single-cell imaging method that reconstructs how a signal CHANGES OVER TIME from fixed-cell snapshots, using DNA content and Geminin to order cells along the cell cycle. Applied to Akt phosphorylation, it uncovers a negative feedback loop that is active only in a narrow window at the G1/S transition; biochemistry points to mTORC1/S6K1-dependent inhibitory phosphorylation of IRS1 as the likely source, though the authors state this edge is not uniquely established. Directly relevant to the question of whether mTOR pathway activity is better described as a time-varying pattern than a fixed level.", "url": "https://mtor-atlas.org/study/GIN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/GIN2026.json" }, { "sid": "CON2021", "title": "Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction", "authors": "Condon KJ; Sabatini DM et al.", "year": 2021, "journal": "Proceedings of the National Academy of Sciences of the United States of America", "doi": "10.1073/pnas.2022120118", "pmid": "33483422", "pmcid": "PMC7848693", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "CRISPR screen; cells", "peer_reviewed": true, "finding": "Genome-wide CRISPR screens reveal AMPK and HRI relay mitochondrial dysfunction to mTORC1.", "url": "https://mtor-atlas.org/study/CON2021/", "api_url": "https://mtor-atlas.org/api/v1/studies/CON2021.json" }, { "sid": "HAR1998", "title": "Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism", "authors": "Hara K; Avruch J et al.", "year": 1998, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.273.23.14484", "pmid": "9603962", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "CHO cells; in vitro", "peer_reviewed": true, "finding": "Amino acid sufficiency signals through mTOR to p70 S6K and 4E-BP1 via a common effector, first linking nutrients to mTOR.", "url": "https://mtor-atlas.org/study/HAR1998/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAR1998.json" }, { "sid": "GAO2026B", "title": "Tumor fat composition predicts response to everolimus and supports low-dose therapy in TSC-associated renal angiomyolipomas: a multicenter prospective study", "authors": "Gao K; Zhang X et al.", "year": 2026, "journal": "Frontiers in oncology", "doi": "10.3389/fonc.2026.1893155", "pmid": "42558341", "pmcid": "PMC13437317", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (TSC-associated renal angiomyolipoma patients, multicenter prospective cohort, n=183)", "peer_reviewed": true, "finding": "In a multicenter prospective cohort of 183 TSC-associated renal angiomyolipoma patients, everolimus reduced tumor volume by >=50% in 44% of patients at 3 months and 83% at 6 months; fat-poor lesions responded significantly better than fat-rich ones. No significant difference in response was detected between the low-dose and standard-dose groups in an exploratory, non-randomised subset, and oral mucositis was less frequent on the low dose; tumor regrowth occurred after treatment discontinuation.", "url": "https://mtor-atlas.org/study/GAO2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAO2026B.json" }, { "sid": "WAN2011", "title": "The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation", "authors": "Wang R; Green DR et al.", "year": 2011, "journal": "Immunity", "doi": "10.1016/j.immuni.2011.09.021", "pmid": "22195744", "pmcid": "PMC3248798", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "The transcription factor Myc drives metabolic reprogramming of activated T cells downstream of mTOR.", "url": "https://mtor-atlas.org/study/WAN2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/WAN2011.json" }, { "sid": "COR2018", "title": "Rapamycin improves healthspan but not inflammaging in nfkb1 mice", "authors": "Correia-Melo C; Birch J; Fielder E; Rahmatika D; Taylor J; Chapman J; Lagnado A; Carroll BM; Miwa S; Richardson G; Jurk D; Oakley F; Mann J; Mann DA; Korolchuk VI; Passos JF", "year": 2018, "journal": "Aging cell", "doi": "10.1111/acel.12882", "pmid": "30468013", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "nfkb1-knockout mice (genetically enhanced NF-kB activity, low-grade chronic inflammation, accelerated ageing); dietary rapamycin", "peer_reviewed": true, "finding": "Separates two effects of rapamycin that are usually assumed to travel together. In mice with genetically enhanced NF-kB activity, rapamycin showed no benefit in lifespan and no reduction of inflammaging, yet still reduced frailty and improved long-term memory, neuromuscular coordination and tissue architecture, with lower markers of cellular senescence. Healthspan benefit is therefore uncoupled here from suppression of inflammation, which is a boundary condition on the common claim that rapamycin acts on ageing mainly by damping inflammation. Note the mixed result: the healthspan outcomes are positive, the lifespan and inflammaging outcomes are null.", "url": "https://mtor-atlas.org/study/COR2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/COR2018.json" }, { "sid": "YAN2017", "title": "Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40", "authors": "Yang H; Pavletich NP et al.", "year": 2017, "journal": "Nature", "doi": "10.1038/nature25023", "pmid": "29236692", "pmcid": "PMC5750076", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Structures reveal how RHEB allosterically activates and PRAS40 inhibits mTORC1.", "url": "https://mtor-atlas.org/study/YAN2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/YAN2017.json" }, { "sid": "SAR2005", "title": "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex", "authors": "Sarbassov DD et al.", "year": 2005, "journal": "Science", "doi": "10.1126/science.1106148", "pmid": "15718470", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells; Drosophila", "peer_reviewed": true, "finding": "The rictor-mTOR complex (mTORC2) directly phosphorylates Akt/PKB on Ser473, regulating cell survival.", "url": "https://mtor-atlas.org/study/SAR2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/SAR2005.json" }, { "sid": "PET2013", "title": "Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases", "authors": "Petit CS; Ferguson SM et al.", "year": 2013, "journal": "The Journal of cell biology", "doi": "10.1083/jcb.201307084", "pmid": "24081491", "pmcid": "PMC3787382", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Folliculin (FLCN) gathers on lysosomes when amino acids are removed and binds RagA directly; FLCN is required for amino acids to recruit mTORC1 to lysosomes via the Rag GTPases.", "url": "https://mtor-atlas.org/study/PET2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/PET2013.json" }, { "sid": "BRU1997", "title": "Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin", "authors": "Brunn GJ; Abraham RT et al.", "year": 1997, "journal": "Science", "doi": "10.1126/science.277.5322.99", "pmid": "9204908", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "HEK293; in vitro", "peer_reviewed": true, "finding": "mTOR directly phosphorylates 4E-BP1 (PHAS-I), releasing eIF4E and establishing mTOR's role in translational control.", "url": "https://mtor-atlas.org/study/BRU1997/", "api_url": "https://mtor-atlas.org/api/v1/studies/BRU1997.json" }, { "sid": "DAL2012", "title": "A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation", "authors": "Dalle Pezze P; Sonntag AG; Thien A; Prentzell MT; Gödel M; Fischer S; Neumann-Haefelin E; Huber TB; Baumeister R; Shanley DP; Thedieck K", "year": 2012, "journal": "Science Signaling", "doi": "10.1126/scisignal.2002469", "pmid": "22457331", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Data-driven dynamic model of the insulin-mTOR network, tested in HeLa and other cell lines", "peer_reviewed": true, "finding": "A time-resolved, data-fitted model of the whole core insulin-mTOR network, including the mTORC1 negative feedback loop onto PI3K. Perturbing it in silico and in cells showed that TSC1-TSC2 is not a regulator of mTORC2, directly or through the feedback loop, and that mTORC2 activation runs through a PI3K variant insensitive to that loop. One of the few places where the feedback loops in the atlas are treated as a dynamical system rather than a diagram.", "url": "https://mtor-atlas.org/study/DAL2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/DAL2012.json" }, { "sid": "SET2011", "title": "TFEB links autophagy to lysosomal biogenesis", "authors": "Settembre C; Di Malta C; Polito VA; Garcia Arencibia M; Vetrini F; Erdin S; et al.; Ballabio A", "year": 2011, "journal": "Science", "doi": "10.1126/science.1204592", "pmid": "21617040", "pmcid": "PMC3638014", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human/mouse cells", "peer_reviewed": true, "finding": "Showed that TFEB drives a coordinated autophagy and lysosomal gene programme during starvation. In this paper TFEB was regulated by ERK2 phosphorylation; its control by mTORC1 at the lysosome was established in later work (SET2012).", "url": "https://mtor-atlas.org/study/SET2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/SET2011.json" }, { "sid": "ARA2009", "title": "mTOR regulates memory CD8 T-cell differentiation", "authors": "Araki K; Ahmed R et al.", "year": 2009, "journal": "Nature", "doi": "10.1038/nature08155", "pmid": "19543266", "pmcid": "PMC2710807", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "mTOR is a key regulator of memory CD8 T-cell differentiation; rapamycin enhances memory responses.", "url": "https://mtor-atlas.org/study/ARA2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/ARA2009.json" }, { "sid": "FU2026", "title": "tRNA-derived fragment tRF-17-8SPOL52 induces resistance to bortezomib in multiple myeloma via autophagy activation.", "authors": "Fu Y; Qiao Z; Xiao Y; Liang T; Xu C", "year": 2026, "journal": "Biochimica et biophysica acta. Molecular basis of disease", "doi": "10.1016/j.bbadis.2026.168396", "pmid": null, "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human (myeloma cell lines + patient samples)", "peer_reviewed": true, "finding": "tRF-17-8SPOL52 tsRNA is upregulated in relapsed/refractory myeloma and drives bortezomib resistance by suppressing RUBCN (a negative autophagy regulator), thereby activating autophagy flux.", "url": "https://mtor-atlas.org/study/FU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/FU2026.json" }, { "sid": "BLA2006", "title": "Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition", "authors": "Blagosklonny MV", "year": 2006, "journal": "Cell Cycle", "doi": "10.4161/cc.5.18.3288", "pmid": "17012837", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Theoretical / review article", "peer_reviewed": true, "finding": "Proposes the 'hyperfunction theory' of aging: TOR signaling, useful in youth, stays switched on into old age and becomes actively damaging.", "url": "https://mtor-atlas.org/study/BLA2006/", "api_url": "https://mtor-atlas.org/api/v1/studies/BLA2006.json" }, { "sid": "KEL2026", "title": "Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage", "authors": "Kell L; Jones EJ; Gharahdaghi N; Wilkinson DJ; Smith K; Atherton PJ; Simon AK; Cox LS; Alsaleh G", "year": 2026, "journal": "Aging Cell", "doi": "10.1111/acel.70364", "pmid": "41524558", "pmcid": "PMC12794675", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human T cells (ex vivo, genotoxic stress); ex vivo aged human immune cells; placebo-controlled experimental medicine study in older adults (low-dose oral rapamycin, in vivo)", "peer_reviewed": true, "finding": "Identifies a previously unrecognized geroprotective mechanism for rapamycin: direct genoprotection. In human T cells exposed to acute genotoxic stress, rapamycin and other mTOR inhibitors suppressed senescence not by slowing protein synthesis, halting cell division, or stimulating autophagy, but by directly reducing DNA lesion burden and improving cell survival. Ex vivo aged human immune cells showed elevated DNA damage, senescence and mTORC-hyperactivation markers. In a placebo-controlled experimental medicine study, low-dose rapamycin significantly reduced p21 (a DNA-damage-induced senescence marker) in immune cells of older adults versus placebo.", "url": "https://mtor-atlas.org/study/KEL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/KEL2026.json" }, { "sid": "SIN2026", "title": "Reduced dietary protein intake does not alter autophagy in human blood: A randomized crossover study in healthy adults", "authors": "Singh S; Fourrier C; Hein LK; Bensalem J; Martin A; Hattersley KJ; King B; Teong XT; Baker K; Lange K; Barker G; Gore JR; Heilbronn LK; Sargeant TJ", "year": 2026, "journal": "Clinical Nutrition", "doi": "10.1016/j.clnu.2026.106778", "pmid": "42721581", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Randomized crossover trial in healthy adults (n=63 completers, mean age ~29.5y); two 4-week interventions (average-protein 20% energy vs reduced-protein 10% energy) separated by a 4-week washout; autophagic flux measured in whole blood/PBMCs via a validated LC3B-II lysosomal-inhibition flux assay", "peer_reviewed": true, "finding": "In a rigorous randomized crossover trial, 63 healthy adults completed both a normal-protein (20% energy) and a reduced-protein (10% energy) diet for 4 weeks each. Despite preclinical evidence that dietary protein restriction should activate autophagy via mTORC1 inhibition, directly measured autophagic flux in blood immune cells did not change between the two diets. This is one of the few human studies to test the protein-restriction-to-autophagy link with a dynamic, flux-based (not just steady-state marker) readout, and the negative result suggests that moderate protein reduction alone, without an accompanying caloric deficit, is not sufficient to engage autophagy in humans the way it does in some animal models.", "url": "https://mtor-atlas.org/study/SIN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SIN2026.json" }, { "sid": "ZHU2026", "title": "LKB1/AMPK deficiency aggravates mitochondrial DNA leakage via mTOR-dependent mitophagy damage in liver injury sensitized by trichloroethylene.", "authors": "Zhu L, Wan C, Li Z, Fan X, Liu Z", "year": 2026, "journal": "Chemico-Biological Interactions", "doi": "10.1016/j.cbi.2026.112261", "pmid": "42462870", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, nominating the LKB1/AMPK/mTOR axis as a candidate therapeutic target in mice; no human data.", "url": "https://mtor-atlas.org/study/ZHU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHU2026.json" }, { "sid": "KIM2012", "title": "SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling", "authors": "Kim YM; Kim DH et al.", "year": 2012, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2012.04.007", "pmid": "22575674", "pmcid": "PMC3389276", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "SH3BP4 negatively regulates amino-acid-Rag-GTPase-mTORC1 signalling.", "url": "https://mtor-atlas.org/study/KIM2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2012.json" }, { "sid": "GU2017", "title": "SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway", "authors": "Gu X; Orozco JM; Saxton RA; Condon KJ; Liu GY; Krawczyk PA; Scaria SM; Harper JW; Gygi SP; Sabatini DM", "year": 2017, "journal": "Science", "doi": "10.1126/science.aao3265", "pmid": "29123071", "pmcid": "PMC5747364", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells (biochemistry)", "peer_reviewed": true, "finding": "Extended nutrient sensing beyond amino acids to METABOLITES: SAMTOR reads S-adenosylmethionine (SAM), the cell's methyl-donor currency, linking methionine and one-carbon metabolism to mTORC1. Relevant to why methionine restriction affects aging.", "url": "https://mtor-atlas.org/study/GU2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/GU2017.json" }, { "sid": "HOS2009", "title": "Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy", "authors": "Hosokawa N; Hara T; Kaizuka T; Kishi C; Takamura A; Miura Y; et al.; Mizushima N", "year": 2009, "journal": "Molecular Biology of the Cell", "doi": "10.1091/mbc.e08-12-1248", "pmid": "19211835", "pmcid": "PMC2663915", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Showed the DIRECT brake mTORC1 uses on autophagy: when nutrients are plentiful, mTORC1 physically joins the ULK1-Atg13-FIP200 complex (the autophagy-starter kinase) and phosphorylates ULK1 to keep it off. Starvation or rapamycin releases this brake and autophagy begins.", "url": "https://mtor-atlas.org/study/HOS2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/HOS2009.json" }, { "sid": "LAN2026", "title": "Rapamycin in Frail Older Subjects with Heart Failure with Preserved Ejection Fraction", "authors": "Lane CM; Mill J; Ellingson P; James I; Borlaug BA; Olson TP; Bagwell MS; Lewis BR; Ingraham BS; Huxley S; Behfar A; Kirkland JL; Lamming DW; Simcox JA; Singh M", "year": 2026, "journal": "Mayo Clinic Proceedings", "doi": "10.1016/j.mayocp.2026.09.006", "pmid": "42759606", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (frail older adults with HFpEF)", "peer_reviewed": true, "finding": "Trial of low-dose rapamycin in frail older adults with heart failure with preserved ejection fraction (HFpEF), from a Mayo Clinic/UW-Madison team including senolytics/mTOR-aging researchers Kirkland and Lamming; abstract not yet available (ahead-of-print).", "url": "https://mtor-atlas.org/study/LAN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAN2026.json" }, { "sid": "YUX2011", "title": "Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling", "authors": "Yu Yonghao; Blenis J et al.", "year": 2011, "journal": "Science", "doi": "10.1126/science.1199484", "pmid": "21659605", "pmcid": "PMC3195509", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Phosphoproteomics identify Grb10 as an mTORC1 substrate driving negative feedback on insulin/PI3K.", "url": "https://mtor-atlas.org/study/YUX2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/YUX2011.json" }, { "sid": "PAN2013", "title": "Amino acid deprivation inhibits TORC1 through a GTPase-activating protein complex for the Rag family GTPase Gtr1", "authors": "Panchaud N; De Virgilio C et al.", "year": 2013, "journal": "Science signaling", "doi": "10.1126/scisignal.2004112", "pmid": "23716719", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Yeast", "peer_reviewed": true, "finding": "The SEACIT complex is a GAP for the Rag/Gtr GTPases mediating amino-acid inhibition of TORC1.", "url": "https://mtor-atlas.org/study/PAN2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/PAN2013.json" }, { "sid": "PLEDGER2026", "title": "Translational repression of 5' TOP mRNAs in chronically activated CD8+ T cells.", "authors": "Pledger ES; Ambavaram N; Ferguson L; Cate JHD", "year": 2026, "journal": "RNA biology", "doi": "10.1080/15476286.2026.2715355", "pmid": "42558000", "pmcid": "PMC13479822", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human (CD8+ T cells in vitro)", "peer_reviewed": true, "finding": "Ribosome profiling of exhausted human CD8+ T cells reveals marked repression of 5'TOP mRNAs despite elevated mTOR activity, uncovering a layer of translational control that overrides or bypasses mTOR in T cell exhaustion.", "url": "https://mtor-atlas.org/study/PLEDGER2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/PLEDGER2026.json" }, { "sid": "LIANG2026", "title": "LINP1 suppresses radiation-induced cellular senescence in keratinocytes by modulating the mTOR-p53 axis", "authors": "Liang X; Hou M; Liu Yaru; Yang Y; Zhang C; Zhang Z; Zhou L", "year": 2026, "journal": "Molecular and Cellular Biochemistry", "doi": "10.1007/s11010-026-05682-z", "pmid": "42593644", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human keratinocytes; ex vivo human skin explants", "peer_reviewed": true, "finding": "LncRNA LINP1 binds the FAT domain of mTOR, reduces mTOR-p53 interaction and p53 Ser15 phosphorylation, thereby suppressing radiation-induced cellular senescence in keratinocytes and human skin.", "url": "https://mtor-atlas.org/study/LIANG2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIANG2026.json" }, { "sid": "DEN2026B", "title": "Multivariate Survival Analysis of a Comprehensive Clinical Trial of Rapamycin in Amyotrophic Lateral Sclerosis Explores Prognostic Factors and Survival Patterns in C9orf72 Carriers", "authors": "De Nardi A; Paris A; Lauria M; Martinelli I; Zucchi E; Simonini C; Mandrioli J; Marchetti L", "year": 2026, "journal": "European Journal of Neurology", "doi": "10.1111/ene.70756", "pmid": "42760861", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (ALS patients, RAP-ALS trial, n=63)", "peer_reviewed": true, "finding": "Secondary, observational survival analysis of the RAP-ALS rapamycin trial (n=63) finds a protective association between rapamycin treatment and survival in C9orf72 mutation carriers (log-rank p=0.026), consistent with a comparison against an independent C9orf72+ cohort (n=40; RMST p=0.04); confounding by indication is not excluded, and the authors flag this as exploratory given the small treated-carrier subgroup (n=6).", "url": "https://mtor-atlas.org/study/DEN2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEN2026B.json" }, { "sid": "MIL2014", "title": "Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction", "authors": "Miller RA; Strong R et al.", "year": 2014, "journal": "Aging cell", "doi": "10.1111/acel.12194", "pmid": "24341993", "pmcid": "PMC4032600", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "Rapamycin's lifespan extension in mice is dose-dependent and greater in females.", "url": "https://mtor-atlas.org/study/MIL2014/", "api_url": "https://mtor-atlas.org/api/v1/studies/MIL2014.json" }, { "sid": "POR2008", "title": "SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth", "authors": "Porstmann T; Schulze A et al.", "year": 2008, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2008.07.007", "pmid": "18762023", "pmcid": "PMC2593919", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "mTORC1 activates SREBP to drive lipogenesis supporting Akt-dependent cell growth.", "url": "https://mtor-atlas.org/study/POR2008/", "api_url": "https://mtor-atlas.org/api/v1/studies/POR2008.json" }, { "sid": "GAN2009", "title": "ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy", "authors": "Ganley IG; Jiang X et al.", "year": 2009, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.M900573200", "pmid": "19258318", "pmcid": "PMC2673298", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "The ULK1-ATG13-FIP200 complex transmits mTOR signalling to initiate autophagy.", "url": "https://mtor-atlas.org/study/GAN2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAN2009.json" }, { "sid": "SUN2026", "title": "Favorable response to second-line sirolimus regardless of status in acquired pure red cell aplasia: A retrospective study from a single center.", "authors": "Sun Z; Jia X; Shen Y et al.", "year": 2026, "journal": "Therapeutic Advances in Hematology", "doi": "10.1177/20406207261483341", "pmid": "42643810", "pmcid": "PMC13504103", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Human (single-centre retrospective, n=58)", "peer_reviewed": true, "finding": "Second-line sirolimus achieved a 54.5% overall response rate in ciclosporin-refractory acquired pure red cell aplasia (64.3% in secondary disease) versus 25.0% for first-line ciclosporin, with responses independent of mutation status. Observational: a single-centre retrospective series with no randomisation and no concurrent control arm. The sirolimus and ciclosporin figures come from different lines of therapy in a selected population, so confounding by indication is not excluded and the two rates should not be read as a head-to-head comparison.", "url": "https://mtor-atlas.org/study/SUN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/SUN2026.json" }, { "sid": "BRU2004", "title": "Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex", "authors": "Brugarolas J; Kaelin WG et al.", "year": 2004, "journal": "Genes & development", "doi": "10.1101/gad.1256804", "pmid": "15545625", "pmcid": "PMC534650", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Hypoxia inhibits mTOR via REDD1-dependent activation of the TSC1/2 complex.", "url": "https://mtor-atlas.org/study/BRU2004/", "api_url": "https://mtor-atlas.org/api/v1/studies/BRU2004.json" }, { "sid": "XU2026B", "title": "The role of mTORC2/RICTOR in immune cells and inflammatory diseases.", "authors": "Xu J; Zhong W; Xin F; Xu F; Zheng Z; Guo F", "year": 2026, "journal": "Inflammation Research", "doi": "10.1007/s00011-026-02365-9", "pmid": "42752901", "pmcid": "PMC13586041", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review of immune cell subsets (T cells, B cells, macrophages, dendritic cells, NK cells) and mouse conditional-knockout models", "peer_reviewed": true, "finding": "mTORC2/RICTOR signaling (via AKT, SGK1, PKC) shapes Th1/Th2 differentiation, Treg stability, memory T cell formation, BCR signaling and plasma cell survival, and macrophage/DC/NK function; its role in tissue inflammation is context-dependent (exacerbating osteoarthritis and pancreatitis but restraining pro-inflammatory polarization in colorectal cancer), and dual mTORC1/2 inhibitors (e.g. AZD2014) show early but complicated promise.", "url": "https://mtor-atlas.org/study/XU2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/XU2026B.json" }, { "sid": "DEM2009", "title": "Rapamycin decelerates cellular senescence", "authors": "Demidenko ZN; Zubova SG; Bukreeva EI; Pospelov VA; Pospelova TV; Blagosklonny MV", "year": 2009, "journal": "Cell Cycle", "doi": "10.4161/cc.8.12.8606", "pmid": "19471117", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human + rodent cell lines", "peer_reviewed": true, "finding": "Blagosklonny's key experiment behind his 'hyperfunction' theory of aging. When a cell's division is blocked but mTOR keeps driving growth, the cell tips into permanent senescence. Rapamycin uncouples the two - keeping arrested cells reversible instead of senescent. Direct evidence that mTOR actively drives the senescent state, not just passively accompanies it.", "url": "https://mtor-atlas.org/study/DEM2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEM2009.json" }, { "sid": "MA2026", "title": "PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling.", "authors": "Ma B; Yu X; Li M; Zhu H; Dong X; Yu S et al.", "year": 2026, "journal": "Translational stroke research", "doi": "10.1007/s12975-026-01474-1", "pmid": "42467322", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse", "peer_reviewed": true, "finding": "PIP4K2A overexpression attenuates cerebral ischemia/reperfusion injury by reducing TRIB3-p62 complex burden and modulating AKT/mTOR signaling to restore autophagic flux, identifying PIP4K2A-AKT/mTOR as a neuroprotective axis in stroke.", "url": "https://mtor-atlas.org/study/MA2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/MA2026.json" }, { "sid": "DUR2012", "title": "Glutaminolysis activates Rag-mTORC1 signaling", "authors": "Duran RV; Hall MN et al.", "year": 2012, "journal": "Molecular cell", "doi": "10.1016/j.molcel.2012.05.043", "pmid": "22749528", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Glutaminolysis activates Rag-mTORC1 signalling through alpha-ketoglutarate production.", "url": "https://mtor-atlas.org/study/DUR2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/DUR2012.json" }, { "sid": "ZHANG2026B", "title": "Dioscorea polystachya Turcz. attenuates male reproductive aging through modulation of mTOR-Beclin-1-mediated autophagy in Leydig and Sertoli cells", "authors": "Zhang Y; Feng J; Xie T; Zhang X; Pan D; Liu S; Zhao D; Wang S; Liu M; Yu S", "year": 2026, "journal": "Journal of Ethnopharmacology", "doi": "10.1016/j.jep.2026.122304", "pmid": "42595064", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Rat (aged model); Mouse Leydig (TM3) and Sertoli (TM4) cells", "peer_reviewed": true, "finding": "Chinese yam protein extract (CYCSE) attenuates male reproductive aging by activating testicular autophagy through the mTOR-Beclin-1 axis in Leydig and Sertoli cells; mTOR activation blocks protective effects.", "url": "https://mtor-atlas.org/study/ZHANG2026B/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZHANG2026B.json" }, { "sid": "LAP2026", "title": "Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size", "authors": "Lapp SC; Kalafut KC; Cissé MY; Tighanimine K; Rosenthal DM; Doxsey W; Hui S; Inouye KE; Morrow CE; Cormerais Y; Manning BD", "year": 2026, "journal": "JCI insight", "doi": "10.1172/jci.insight.210523", "pmid": "42720990", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "SkM-TSC2-5A knock-in mice (AKT-phosphorylation-resistant TSC2, skeletal muscle-specific) vs SkM-TSC2-WT littermates, both sexes", "peer_reviewed": true, "finding": "Using a mouse model expressing an AKT-nonphosphorylatable TSC2 mutant specifically in skeletal muscle, the Manning lab genetically separated feeding-induced from contraction-induced mTORC1 activation. AKT-mediated TSC2 phosphorylation is required for feeding (but not contraction) to activate muscle mTORC1 and drive postprandial protein synthesis — yet mice lacking this feeding-induced signal have normal muscle mass and myofiber size, and instead show improved maximal endurance capacity with a modest rise in mitochondrial content. The finding dissociates mTORC1's role in postprandial anabolism from its role in maintaining steady-state muscle mass, and is a directly relevant data point for whether the pattern/source of mTORC1 activation (feeding vs. mechanical) — not just its average level — shapes downstream outcomes.", "url": "https://mtor-atlas.org/study/LAP2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LAP2026.json" }, { "sid": "TEE2003", "title": "Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb", "authors": "Tee AR; Cantley LC et al.", "year": 2003, "journal": "Current Biology", "doi": "10.1016/s0960-9822(03)00506-2", "pmid": "12906785", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cell lines", "peer_reviewed": true, "finding": "TSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and activates mTOR signalling.", "url": "https://mtor-atlas.org/study/TEE2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/TEE2003.json" }, { "sid": "ARI2015", "title": "Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy", "authors": "Arias E; Koga H; Diaz A; Mocholi E; Patel B; Cuervo AM", "year": 2015, "journal": "Mol Cell", "doi": "10.1016/j.molcel.2015.05.030", "pmid": "26118642", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse liver, rat liver, cell lines (NIH 3T3)", "peer_reviewed": true, "finding": "Extends the mTOR-autophagy relationship to a third form of autophagy that the Atlas otherwise does not cover, and reverses two of its usual terms. Here it is mTORC2, not mTORC1, that sits on the lysosomal membrane, and it inhibits chaperone-mediated autophagy through Akt, while the phosphatase PHLPP1 counteracts it; the balance controls assembly and disassembly of the translocation complex that pulls single proteins into the lysosome. Boundary: mechanism in cells and rodent liver; the claim that restoring this axis helps in ageing or disease is proposed, not tested here.", "url": "https://mtor-atlas.org/study/ARI2015/", "api_url": "https://mtor-atlas.org/api/v1/studies/ARI2015.json" }, { "sid": "ALI2022", "title": "The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis", "authors": "Ali ES; Lipońska A; O'Hara BP; Amici DR; Torno MD; Gao P; Asara JM; Yap MF; Mendillo ML; Ben-Sahra I", "year": 2022, "journal": "Molecular Cell", "doi": "10.1016/j.molcel.2022.06.008", "pmid": "35772404", "pmcid": "PMC9444906", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cells; xenograft tumors", "peer_reviewed": true, "finding": "Building a nucleotide needs a carbon donor, and cells get it from bicarbonate dissolved in their surroundings. This study shows mTORC1 does not just switch on the nucleotide enzymes - it also arranges the delivery of the raw material. Through S6K and the translation factor eIF4B, mTORC1 selectively increases translation of the mRNA for SLC4A7, a sodium-bicarbonate cotransporter, so more bicarbonate is pulled into the cell. Removing SLC4A7 from cells with hyperactive mTORC1 cut flux through both de novo purine and pyrimidine synthesis and slowed cell and tumor growth, without changing intracellular pH - so the transporter matters as a supply line, not as a pH regulator. A fourth distinct route by which mTORC1 feeds nucleotide synthesis, alongside CAD (BEN2013), the mitochondrial folate cycle (BEN2016) and demand coupling (VAL2017).", "url": "https://mtor-atlas.org/study/ALI2022/", "api_url": "https://mtor-atlas.org/api/v1/studies/ALI2022.json" }, { "sid": "STO2003", "title": "Rheb is an essential regulator of S6K in controlling cell growth in Drosophila", "authors": "Stocker H; Hafen E et al.", "year": 2003, "journal": "Nature cell biology", "doi": "10.1038/ncb995", "pmid": "12766775", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Drosophila", "peer_reviewed": true, "finding": "Rheb is an essential regulator of S6K controlling cell growth downstream of TSC in Drosophila.", "url": "https://mtor-atlas.org/study/STO2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/STO2003.json" }, { "sid": "LEE2026", "title": "Aberrant excitatory neuronal ERBB4 promotes Alzheimer's disease pathology", "authors": "Lee SY; Park E; Lee HE; Kim S; Yeo Y; Park J; Choi YJ; Lee K; Yoon KJ; Park S; Kim E; Kim JI; Chung WS", "year": 2026, "journal": "Nature", "doi": "10.1038/s41586-026-10964-z", "pmid": "42649291", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse AD models (5xFAD/APP), excitatory-neuron-specific Erbb4 deletion and overexpression; human AD single-nucleus transcriptomics", "peer_reviewed": true, "finding": "Ectopic ERBB4 in excitatory neurons is one of the earliest changes in AD mouse models and is necessary for synapse loss, reactive gliosis, amyloid plaque deposition and cognitive deficits in AD mice, and its overexpression in wild-type excitatory neurons is sufficient to reproduce synapse loss, gliosis and cognitive deficits (but not amyloid plaques); these effects require mTOR signalling downstream of ERBB4.", "url": "https://mtor-atlas.org/study/LEE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LEE2026.json" }, { "sid": "HAR2009", "title": "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice", "authors": "Harrison DE et al.", "year": 2009, "journal": "Nature", "doi": "10.1038/nature08221", "pmid": "19587680", "pmcid": "PMC2786175", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (genetically heterogeneous, 3 sites)", "peer_reviewed": true, "finding": "Rapamycin fed from 600 days of age extended median and maximal lifespan in both sexes; age at 90% mortality rose 14% in females and 9% in males.", "url": "https://mtor-atlas.org/study/HAR2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAR2009.json" }, { "sid": "REN2026", "title": "Microbiota-associated kynurenic acid drives PD-1 blockade resistance through an ITGA2-mTOR-CTSV axis in gastric cancer.", "authors": "Ren Y; Yu X; Jiang J; Luo J; Zhao C; et al.", "year": 2026, "journal": "Journal for immunotherapy of cancer", "doi": "10.1136/jitc-2026-015172", "pmid": "42562425", "pmcid": "PMC13448627", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mouse + Human (gastric cancer)", "peer_reviewed": true, "finding": "Tumor microbiota-derived kynurenic acid drives resistance to PD-1 blockade in gastric cancer through the ITGA2-mTOR-CTSV axis: kynurenic acid induces ITGA2 and inhibits an mTOR-dependent cascade, which sustains cathepsin V expression and suppresses CD8+ T cell cytotoxic function.", "url": "https://mtor-atlas.org/study/REN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/REN2026.json" }, { "sid": "ZID2009", "title": "4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila", "authors": "Zid BM; Rogers AN; Katewa SD; Vargas MA; Kolipinski MC; Lu TA; Benzer S; Kapahi P", "year": 2009, "journal": "Cell", "doi": "10.1016/j.cell.2009.07.034", "pmid": "19804760", "pmcid": "PMC2759400", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Drosophila (fruit fly)", "peer_reviewed": true, "finding": "Connected the dots between diet, mTOR, and lifespan. 4E-BP, an mTOR target, is upregulated on dietary restriction and here was shown to be REQUIRED for the lifespan boost, working by selectively boosting translation of mitochondrial genes. A rare case pinning a specific mTOR effector to the longevity benefit of eating less.", "url": "https://mtor-atlas.org/study/ZID2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/ZID2009.json" }, { "sid": "JIB2026", "title": "Rapamycin co-exposure fails to reduce cisplatin-induced damage in GC6-spg spermatogonial cell line.", "authors": "Jibrin A, Mitchell RT, Lopes F", "year": 2026, "journal": "Reproduction & Fertility", "doi": "10.1530/RAF-26-0044", "pmid": "42455795", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Negative_result", "model_system": "GC6-spg spermatogonial cell line", "peer_reviewed": true, "finding": "Rapamycin did not protect a mouse spermatogonial cell line from cisplatin damage in vitro, unlike reports in female fertility models.", "url": "https://mtor-atlas.org/study/JIB2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/JIB2026.json" }, { "sid": "KIM2011", "title": "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1", "authors": "Kim J; Kundu M; Viollet B; Guan KL", "year": 2011, "journal": "Nature Cell Biology", "doi": "10.1038/ncb2152", "pmid": "21258367", "pmcid": "PMC3987946", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human/mouse cells", "peer_reviewed": true, "finding": "Revealed the tug-of-war over ULK1: the energy sensor AMPK phosphorylates ULK1 at activating sites to turn autophagy ON when energy is low, while mTORC1 phosphorylates a different site (Ser757) to keep it OFF and even blocks AMPK from reaching ULK1. Two opposing kinases wired to the same switch.", "url": "https://mtor-atlas.org/study/KIM2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/KIM2011.json" }, { "sid": "LIP2017", "title": "Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy", "authors": "Lipton JO; Boyle LM; Yuan ED; Hochstrasser KJ; Chifamba FF; Nathan A; Tsai PT; Davis F; Sahin M", "year": 2017, "journal": "Cell Reports", "doi": "10.1016/j.celrep.2017.07.008", "pmid": "28746872", "pmcid": "PMC5603761", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse models of tuberous sclerosis complex (Tsc1/Tsc2 loss)", "peer_reviewed": true, "finding": "In mouse models of tuberous sclerosis, where mTOR is stuck on, the circadian clock ran abnormally: poor timekeeping in constant conditions and exaggerated responses to phase resetting. mTOR raised BMAL1 levels by changing its translation, degradation and location; genetically lowering BMAL1 rescued the behavioural rhythm defects. Constant, unpatterned mTOR activity disturbs a rhythm downstream.", "url": "https://mtor-atlas.org/study/LIP2017/", "api_url": "https://mtor-atlas.org/api/v1/studies/LIP2017.json" }, { "sid": "POU2013", "title": "High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition", "authors": "Poulsen MM et al.", "year": 2013, "journal": "Diabetes", "doi": "10.2337/db12-0975", "pmid": "23193181", "pmcid": "PMC3609591", "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Negative_result", "model_system": "Humans, RCT, obese men (n=24)", "peer_reviewed": true, "finding": "4 weeks of high-dose resveratrol had no effect on insulin sensitivity, blood pressure, or body composition - directly contradicting the promising rodent data that drove the original hype.", "url": "https://mtor-atlas.org/study/POU2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/POU2013.json" }, { "sid": "THE2026", "title": "mTORC1 supports progression toward activation competence in quiescent adult neural stem cells", "authors": "Thetiot M; Bally-Cuif L et al.", "year": 2026, "journal": "bioRxiv", "doi": "10.64898/2026.05.04.722648", "pmid": null, "pmcid": null, "evidence": { "code": "PP", "label": "Preprint, not peer-reviewed", "note": "this describes the kind of study, not its quality" }, "category": "Preprint", "model_system": "Adult zebrafish pallium neural stem cells; in situ analysis and single-cell RNA-seq", "peer_reviewed": false, "finding": "In the adult zebrafish brain, mTORC1 activity is enriched during a long quiescence phase in which neural stem cells become able to activate; perturbing mTORC1 changes how cells progress through this phase, setting the tempo of the move towards activation while preserving stemness. Preprint, not peer-reviewed.", "url": "https://mtor-atlas.org/study/THE2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/THE2026.json" }, { "sid": "STU2018", "title": "Architecture of the human mTORC2 core complex", "authors": "Stuttfeld E; Ban N et al.", "year": 2018, "journal": "eLife", "doi": "10.7554/eLife.33101", "pmid": "29424687", "pmcid": "PMC5837792", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Cryo-EM structure", "peer_reviewed": true, "finding": "Architecture of the human mTORC2 core complex (mTOR-Rictor-SIN1-mLST8).", "url": "https://mtor-atlas.org/study/STU2018/", "api_url": "https://mtor-atlas.org/api/v1/studies/STU2018.json" }, { "sid": "KUS2026", "title": "CASTOR1 regulates humoral immune responses and contributes to the pathogenesis of systemic lupus erythematosus", "authors": "Kusuda T; Komai T; Itamiya T; Abe T; Okamura T; Fujio K", "year": 2026, "journal": "Arthritis & Rheumatology", "doi": "10.1002/art.70314", "pmid": "42695806", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human B cells (ImmuNexUT transcriptomes, n=136 SLE patients) + whole-body and B cell-specific Castor1-knockout mice", "peer_reviewed": true, "finding": "Gives the arginine sensor CASTOR1 a defined physiological job upstream of mTORC1: losing it de-represses mTORC1 in B cells and drives plasma-cell expansion, IgG and anti-dsDNA autoantibodies, and lupus-like glomerulonephritis. In human SLE, CASTOR1 expression in plasmablasts was inversely correlated with disease activity (r = -0.32, p = 0.00031). One of the few studies to tie a specific upstream amino-acid sensor to a human autoimmune phenotype rather than to cancer or growth.", "url": "https://mtor-atlas.org/study/KUS2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/KUS2026.json" }, { "sid": "MA2005", "title": "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis", "authors": "Ma L; Chen Z; Erdjument-Bromage H; Tempst P; Pandolfi PP", "year": 2005, "journal": "Cell", "doi": "10.1016/j.cell.2005.02.031", "pmid": "15851026", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "The MAPK input to mTORC1. In mammalian cells, ERK phosphorylates TSC2 and inactivates the TSC complex, so growth signalling through Ras/ERK converges on the same brake that Akt releases. This is the third major upstream arm alongside PI3K/Akt and AMPK. Its practical significance is that it offers a route to mTORC1 activation that PI3K inhibitors do not close - though that inference is mechanistic; no human data here.", "url": "https://mtor-atlas.org/study/MA2005/", "api_url": "https://mtor-atlas.org/api/v1/studies/MA2005.json" }, { "sid": "NCT05835999", "title": "Everolimus Aging Study (EVERLAST): Clinical Evaluation of mTORC1 Inhibition for Geroprotection", "authors": "University of Wisconsin, Madison (registered trial)", "year": null, "journal": "ClinicalTrials.gov (registration)", "doi": "NCT05835999", "pmid": null, "pmcid": null, "evidence": { "code": "RT", "label": "Registered trial, no results yet", "note": "this describes the kind of study, not its quality" }, "category": "Ongoing_Trial", "model_system": "Humans, RCT (registered, ongoing)", "peer_reviewed": false, "finding": "Currently active phase 2 trial (NCT05835999) directly testing this Atlas's open dosing hypothesis: whether daily low-dose (0.5mg) versus weekly (5mg) everolimus can improve aging biomarkers and insulin resistance in humans without the metabolic penalty seen with continuous higher-dose rapalog use. No results yet - status ACTIVE_NOT_RECRUITING.", "url": "https://mtor-atlas.org/study/NCT05835999/", "api_url": "https://mtor-atlas.org/api/v1/studies/NCT05835999.json" }, { "sid": "NOJ2003", "title": "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif", "authors": "Nojima H; Yonezawa K et al.", "year": 2003, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.C200665200", "pmid": "12604610", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro", "peer_reviewed": true, "finding": "Raptor binds mTOR substrates via their TOS motifs, acting as the substrate-presenting scaffold of mTORC1.", "url": "https://mtor-atlas.org/study/NOJ2003/", "api_url": "https://mtor-atlas.org/api/v1/studies/NOJ2003.json" }, { "sid": "HAL2026", "title": "5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling", "authors": "Halle JL; Zhang Q; Jenkins T; Carson JA", "year": 2026, "journal": "American Journal of Physiology-Cell Physiology", "doi": "10.1152/ajpcell.00321.2026", "pmid": "42734427", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "C2C12 mouse myotubes (in vitro), with and without CT26 colon-tumor-cell-conditioned media", "peer_reviewed": true, "finding": "FOLFOX and oxaliplatin disrupted mTORC1/AMPK regulation of autophagy flux and protein synthesis in cultured myotubes; the effect was not easily reversible on drug withdrawal. Rapamycin (but not metformin) restored autophagy flux and AMPK phosphorylation, though without restoring protein synthesis.", "url": "https://mtor-atlas.org/study/HAL2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAL2026.json" }, { "sid": "DEN2026", "title": "Spalt-related is an inhibitor of mTORC1-mediated growth activated by the integrated stress response", "authors": "Onur Deniz, Ying Liu, Tuuli Kirkinen, Krista Kokki, Kateryna Gaertner, Pau Clavell-Revelles, Jaakko Mattila, Ville Hietakangas", "year": 2026, "journal": "The EMBO Journal", "doi": "10.1038/s44318-026-00858-1", "pmid": "42436355", "pmcid": null, "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Drosophila melanogaster", "peer_reviewed": true, "finding": "Transcription factor Spalt-related (Salr) is a novel mTORC1 inhibitor in Drosophila activated by the integrated stress response, restricting anabolic growth and lipid storage during nutrient stress. Salr responds to a distinct, ISR-driven cue, acting convergently with FoxO rather than downstream of it.", "url": "https://mtor-atlas.org/study/DEN2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/DEN2026.json" }, { "sid": "HE2025", "title": "mTORC1, the maestro of cell metabolism and growth", "authors": "He L; Cho S; Blenis J", "year": 2025, "journal": "Genes & Development", "doi": "10.1101/gad.352084.124", "pmid": "39572234", "pmcid": "PMC11789495", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "N/A (narrative review)", "peer_reviewed": true, "finding": "Comprehensive current review of how nutrients and growth signals are integrated by mTORC1 and the metabolic programs it commands, plus the clinical outlook for mTORC1-targeted therapy across cancer, neurodegeneration, obesity, diabetes and aging -- anchor reference for the pathway map.", "url": "https://mtor-atlas.org/study/HE2025/", "api_url": "https://mtor-atlas.org/api/v1/studies/HE2025.json" }, { "sid": "FRA2013", "title": "Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial", "authors": "Franz DN; Belousova E; Sparagana S; Bebin EM; Frost M; et al.; Jozwiak S", "year": 2013, "journal": "Lancet", "doi": "10.1016/S0140-6736(12)61134-9", "pmid": "23158522", "pmcid": null, "evidence": { "code": "H", "label": "Human study", "note": "this describes the kind of study, not its quality" }, "category": "Human", "model_system": "Humans, phase 3 RCT (n=117, TSC)", "peer_reviewed": true, "finding": "Phase 3 RCT (n=117) in tuberous sclerosis, the disease where mTOR is stuck ON by a genetic fault. Everolimus shrank brain tumors (SEGA) by >=50% in 35% of patients versus 0% on placebo. Because the underlying cause here is direct mTOR overactivation, this is arguably the cleanest randomised human evidence that blocking mTOR works in a genetically defined mTORopathy -- which does not extend to mTOR inhibition in people without such a mutation.", "url": "https://mtor-atlas.org/study/FRA2013/", "api_url": "https://mtor-atlas.org/api/v1/studies/FRA2013.json" }, { "sid": "GAN2011", "title": "Evidence for direct activation of mTORC2 kinase activity by phosphatidylinositol 3,4,5-trisphosphate", "authors": "Gan X; Wu D et al.", "year": 2011, "journal": "The Journal of biological chemistry", "doi": "10.1074/jbc.M110.195016", "pmid": "21310961", "pmcid": "PMC3064154", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "In vitro; cells", "peer_reviewed": true, "finding": "PIP3 directly stimulates mTORC2 kinase activity, linking PI3K to mTORC2.", "url": "https://mtor-atlas.org/study/GAN2011/", "api_url": "https://mtor-atlas.org/api/v1/studies/GAN2011.json" }, { "sid": "GOB2016", "title": "Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot", "authors": "Goberdhan DC; Harris AL et al.", "year": 2016, "journal": "Cell metabolism", "doi": "10.1016/j.cmet.2016.03.013", "pmid": "27076075", "pmcid": "PMC5067300", "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Review: intracellular amino-acid transporters mark the site of mTORC1 activation.", "url": "https://mtor-atlas.org/study/GOB2016/", "api_url": "https://mtor-atlas.org/api/v1/studies/GOB2016.json" }, { "sid": "ABR2026", "title": "Molecular switches of SQSTM1: the impact of post-translational modifications on autophagy and neurodegeneration", "authors": "Abrar F; Martin DDO", "year": 2026, "journal": "Autophagy", "doi": "10.1080/15548627.2026.2711593", "pmid": "42560011", "pmcid": null, "evidence": { "code": "R", "label": "Review — secondary literature, not a new result", "note": "this describes the kind of study, not its quality" }, "category": "Review", "model_system": "Review", "peer_reviewed": true, "finding": "Comprehensive review of how post-translational modifications (phosphorylation, ubiquitination, acetylation, S-acylation, S-nitrosylation) tune SQSTM1/p62's role as the autophagy cargo-receptor hub -- relevant to neurodegenerative disease (Alzheimer's, ALS, Huntington's) where SQSTM1 regulation goes awry.", "url": "https://mtor-atlas.org/study/ABR2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/ABR2026.json" }, { "sid": "HAN2012", "title": "Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway", "authors": "Han JM; Kim S et al.", "year": 2012, "journal": "Cell", "doi": "10.1016/j.cell.2012.02.044", "pmid": "22424946", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Mammalian cells", "peer_reviewed": true, "finding": "Leucyl-tRNA synthetase acts as an intracellular leucine sensor activating mTORC1 via the Rag pathway.", "url": "https://mtor-atlas.org/study/HAN2012/", "api_url": "https://mtor-atlas.org/api/v1/studies/HAN2012.json" }, { "sid": "LU2026", "title": "Mathematical Modeling of Dietary Timing- and Protein Quality-Responsive Liver Circadian Clock and its Function on Ribosome Biogenesis", "authors": "Lu L; Levy JL; Anthony TG; Androulakis IP", "year": 2026, "journal": "Physiological Genomics", "doi": "10.1152/physiolgenomics.00152.2026", "pmid": "42647400", "pmcid": null, "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Semi-mechanistic computational model of mammalian liver (peripheral clock, mTORC1, GCN2-ISR, ribosome biogenesis)", "peer_reviewed": true, "finding": "Builds a semi-mechanistic model in which liver mTORC1 and GCN2-ISR signalling are driven by RHYTHMS in dietary essential amino acid availability rather than by a fixed nutrient level. Simulations show the two pathways jointly set metabolic entrainability and are required to keep the peripheral clock and ribosome biogenesis synchronised under nutrient stress, and predict individualised recovery trajectories after a transient dietary disruption. A worked example of treating mTORC1 activity as a time-varying pattern whose shape — not just its average — determines the downstream growth output.", "url": "https://mtor-atlas.org/study/LU2026/", "api_url": "https://mtor-atlas.org/api/v1/studies/LU2026.json" }, { "sid": "CHE2009", "title": "mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells", "authors": "Chen C; Zheng P et al.", "year": 2009, "journal": "Science signaling", "doi": "10.1126/scisignal.2000559", "pmid": "19934433", "pmcid": "PMC4020596", "evidence": { "code": "A", "label": "Animal model", "note": "this describes the kind of study, not its quality" }, "category": "Animal", "model_system": "Mouse (HSC)", "peer_reviewed": true, "finding": "mTOR hyperactivation drives HSC aging; rapamycin restores hematopoietic stem-cell function.", "url": "https://mtor-atlas.org/study/CHE2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/CHE2009.json" }, { "sid": "PET2009", "title": "DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival", "authors": "Peterson TR; Laplante M; Thoreen CC; Sancak Y; Kang SA; Kuehl WM; Gray NS; Sabatini DM", "year": 2009, "journal": "Cell", "doi": "10.1016/j.cell.2009.03.046", "pmid": "19446321", "pmcid": "PMC2758791", "evidence": { "code": "M", "label": "Molecular — cells, biochemistry, structure", "note": "this describes the kind of study, not its quality" }, "category": "Mechanism", "model_system": "Human cancer cell lines", "peer_reviewed": true, "finding": "Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling ON - a neat example of how an 'inhibitor' can be co-opted by cancer.", "url": "https://mtor-atlas.org/study/PET2009/", "api_url": "https://mtor-atlas.org/api/v1/studies/PET2009.json" } ] }