Topics

The Atlas indexes 146 topics — genes and proteins, complexes, drugs, diseases, processes, outcomes. 46 have a page of their own; the rest are indexed and searchable but not written up, because a page with nothing on it but a name is worse than no page.

146 topics

Genes & proteins 63

mTOR 64 Serine/threonine kinase; central regulator of cell growth and metabolism; direct target of rapamycin.
Akt/PKB 13 Key kinase downstream of PI3K in growth signaling; activated by mTORC2.
AMPK 9 AMP-activated protein kinase; cellular energy sensor; inhibits mTORC1 under low-energy conditions.
S6K1 9 Direct downstream effector of mTORC1 controlling protein synthesis, and the source of the pathway's main negative feedback: S6K1 phosphorylates and represses IRS-1, uncoupling the insulin receptor from PI3K (HAR2004, SHA2004). Its deletion extends lifespan in FEMALE mice (+19% median, not significant in males; SEL2009) and protects against diet-induced obesity.
TSC1/TSC2 9 Tuberin-hamartin tumor suppressor complex; acts as a GTPase-activating protein for Rheb; integrates growth-factor and energy signals to control mTORC1.
Rheb 8 Small GTPase that directly activates mTORC1 when in its GTP-bound state; held inactive by TSC1/TSC2.
4E-BP1 7 Translational repressor; the master effector through which mTORC1 controls protein synthesis. mTORC1 phosphorylates 4E-BP1 to release eIF4E and switch translation ON.
Raptor 7 Defining subunit of mTORC1; scaffold that presents substrates (S6K1, 4E-BP1) to mTOR. Its presence is what makes a complex 'mTORC1'.
PI3K 6 Phosphoinositide 3-kinase; produces signaling lipids downstream of growth-factor receptors; activates Akt and sits upstream of the entire mTOR pathway.
Rag GTPases 5 Family of small GTPases that let mTORC1 sense amino acids by controlling its localization near its activator Rheb inside the cell.
SLC38A9 5 Lysosomal amino-acid transporter and signaling component; acts as an arginine sensor on the lysosomal membrane. Works together with v-ATPase and Ragulator to relay luminal arginine availability to the Rag GTPases and thereby recruit mTORC1. Loss of SLC38A9 impairs arginine-dependent mTORC1 activation.
ULK1 5 Initiator of autophagy; target of mTORC1 inhibition and AMPK activation.
eIF4E 4 Cap-binding protein that recruits the ribosome to an mRNA. Held hostage by 4E-BP1 until mTORC1 phosphorylates the latter - the rate-limiting step of cap-dependent translation.
TFEB 4 Master transcription factor for lysosome biogenesis and autophagy. mTORC1 phosphorylates TFEB to trap it in the cytosol; when mTORC1 is off, TFEB enters the nucleus and turns on the cell's recycling program.
FLCN / FNIP1/2 3 Folliculin and its binding partners FNIP1/2; act as a GTPase-activating protein (GAP) for RagC/D, switching the Rag heterodimer into the configuration that recruits mTORC1 to the lysosome. FLCN-FNIP complements the GATOR1/GATOR2 arm by regulating the RagC/D half of the cycle. Loss of FLCN causes Birt-Hogg-Dube syndrome through a SUBSTRATE-SPECIFIC defect rather than blanket mTORC1 hyperactivation: canonical outputs (S6K1, 4E-BP1) are largely preserved, while TFEB and TFE3 escape phosphorylation and accumulate in the nucleus (NAP2020).
FoxO 3 Forkhead box O transcription factors (FOXO1/3/4) that act as key downstream targets of mTORC1/Akt signalling; phosphorylation by Akt excludes them from the nucleus, while mTORC1 inhibition promotes nuclear translocation and transcription of stress-response and longevity genes.
IRS-1 / IRS-2 3 Insulin receptor substrate proteins - the adaptors that carry the signal from the insulin/IGF-1 receptor to PI3K. S6K1 phosphorylates and represses them, which is the pathway's principal negative feedback loop: sustained mTORC1 activity deafens the cell to insulin, and blocking mTOR restores insulin signalling and raises Akt activity.
p62/SQSTM1 3 Autophagy cargo receptor and mTORC1-activating scaffold on lysosomes; elevated p62 accumulation indicates impaired autophagic flux.
Rictor 3 Defining subunit of mTORC2 (Rapamycin-Insensitive Companion of mTOR); routes mTOR toward Akt and the cytoskeleton rather than S6K1/4E-BP1.
CASTOR1 2 Direct cytosolic arginine sensor for the mTORC1 pathway; arginine binding releases its inhibition of GATOR2.
ERK / RSK (MAPK) 2 The Ras-MAPK growth-signalling arm. ERK and its effector RSK phosphorylate TSC2 and inactivate the TSC complex, so MAPK signalling converges on the same brake that Akt releases (MA2005). This is the third major upstream input to mTORC1 alongside PI3K/Akt and AMPK, and it is a route to mTORC1 activation that PI3K inhibitors do not close. mTORC1 inhibition also feeds back to activate MAPK (CAR2008).
FKBP12 2 Rapamycin's docking protein. Rapamycin first binds FKBP12; only the FKBP12-rapamycin pair can grab mTOR. This is why rapamycin is an 'allosteric' (indirect) inhibitor - it works through a chaperone, not by blocking the active site.
Grb10 2 mTORC1 substrate that, once phosphorylated, damps insulin/IGF-1 receptor signalling - one arm of the negative feedback that makes mTOR inhibitors paradoxically raise upstream Akt activity.
mLST8 2 mLST8 (GbetaL) - a shared subunit of BOTH mTOR complexes. Especially required for mTORC2 to assemble and signal to Akt; largely dispensable for mTORC1.
PTEN 2 Phosphatase that erases PIP3 and so shuts down the PI3K arm. One of the most frequently lost tumour suppressors in human cancer, and the commonest way this pathway gets stuck on.
SAMTOR 2 Sensor of S-adenosylmethionine (SAM), linking methionine / one-carbon metabolism to mTORC1 via GATOR1.
Sestrin2 2 Direct intracellular leucine sensor and a NEGATIVE regulator of mTORC1. When leucine is scarce, Sestrin2 binds and inhibits GATOR2, so GATOR1 stays active and keeps mTORC1 switched off. Leucine binding (~20 uM affinity) releases GATOR2 - the pathway is switched on by removing a brake, not by adding a signal. Sestrin2 does not act on the Rag GTPases directly; it works two steps upstream, through GATOR2 and GATOR1.
Atg5 1 Core gene required for autophagosome formation; overexpressing it in mice is sufficient to extend lifespan on its own.
Beclin-1 (BECN1) 1 Core autophagy protein required for autophagosome nucleation; regulated by mTOR and inhibited by Bcl-2 family members.
DEPTOR 1 Endogenous inhibitor of both mTORC1 and mTORC2; paradoxically overexpressed in a subset of multiple myelomas.
eIF4A 1 ATP-dependent RNA helicase that unwinds 5' mRNA secondary structures; activated downstream of mTORC1 to promote selective cap-dependent translation initiation.
FGF21 1 Fibroblast growth factor 21, a metabolic hormone that activates AMPK/mTOR signaling to regulate glucose metabolism and wound healing.
GADD45alpha 1 Stress-inducible DNA repair protein regulated downstream of the mTOR-TFEB axis; restoration of its expression by TFEB activation confers protection against nephrotoxicity.
ITGA2 (Integrin alpha-2) 1 Integrin subunit alpha-2; found to mediate kynurenic acid-driven mTOR activation in the ITGA2-mTOR-CTSV immunotherapy resistance axis in gastric cancer.
LARS (leucyl-tRNA synthetase) 1 Enzyme that charges tRNA with leucine, proposed as an alternative intracellular leucine sensor acting as a GAP for RagD. Competes with the Sestrin2 model - an unresolved question in the field.
LC3B (MAP1LC3B) 1 Key autophagosome membrane marker; lipidation of LC3B (LC3-II) is induced when mTOR is inhibited and marks autophagy induction.
LKB1 (STK11) 1 A serine/threonine kinase that activates AMPK and acts upstream of mTOR to regulate cellular energy sensing, autophagy, and metabolism.
P-glycoprotein (ABCB1) 1 Multidrug resistance efflux transporter encoded by ABCB1; selectively upregulated at the translational level by mTOR-eIF4A signaling under oxidative stress.
PDCD4 1 Translation inhibitor that blocks the eIF4A helicase. S6K1 marks it for degradation, giving mTORC1 a second, 4E-BP-independent route to raising protein synthesis.
PIK3CA 1 Phosphatidylinositol 3-kinase catalytic subunit alpha; its activating mutations (e.g. E545K, H1047R) frequently drive AKT/mTOR pathway hyperactivation in cancer.
PIP4K2A 1 Phosphatidylinositol-5-phosphate 4-kinase type II alpha; regulates autophagy and AKT/mTOR signaling and is neuroprotective in cerebral ischemia/reperfusion models.
PRAS40 1 Insulin-regulated inhibitor subunit of mTORC1. Insulin triggers Akt to phosphorylate PRAS40, releasing its brake and switching mTORC1 on.
REDD1 (DDIT4) 1 Hypoxia-induced protein that suppresses mTORC1 through the TSC complex - the mechanism by which low oxygen and low growth factors share a single brake.
RUBCN (Rubicon) 1 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein; a negative regulator of autophagy whose suppression activates autophagic flux.
SLC15A3 1 A lysosomal dipeptide transporter that imports dipeptides to sustain mTORC1 activation and can confer antimetabolite chemotherapy resistance in lymphoma.
Spalt-related (Salr) 1 Transcription factor in Drosophila identified as a novel inhibitor of mTORC1-mediated growth, activated by the integrated stress response to restrict anabolic processes during nutrient stress.
TBC1D7 1 Third constitutive subunit of the TSC complex; its loss weakens but does not abolish TSC1-TSC2 function.
TNKS2 (Tankyrase-2) 1 Tankyrase-2, a PARP family enzyme; its loss activates AMPK and suppresses mTORC1, impairing adipocyte differentiation.
USP7 1 Ubiquitin-specific protease 7, a deubiquitinase that modulates the TSC1/mTOR axis and promotes renal fibrosis via stabilization of KDM5B.
v-ATPase 1 Vacuolar H+-ATPase; senses lysosomal amino acids from the inside and relays the signal to Ragulator-Rag to activate mTORC1.
alpha-synuclein (SNCA) 0 Presynaptic protein whose misfolded aggregates form Lewy bodies in Parkinson's disease and related synucleinopathies. Cleared primarily by autophagy/chaperone-mediated autophagy; mTORC1 inhibition promotes its clearance while chronic pan-mTOR inhibition risks the mTORC2-dependent synaptic-plasticity cost noted in gap H8.
ASCL1 0 Achaete-scute homolog 1, a bHLH transcription factor that acts upstream of a CCNB1/mTOR axis in renal injury.
ErbB3 (HER3) 0 Receptor tyrosine kinase that is one of the most potent upstream activators of PI3K/AKT/mTOR signalling.
HIF-1α 0 Hypoxia-inducible factor 1-alpha, the master transcription factor for metabolic and angiogenic responses to low oxygen, and an mTOR-independent target of rapamycin in aged tissue.
IRS1 / IRS2 0 Insulin receptor substrate proteins 1 and 2; scaffold adaptors that couple the insulin/IGF-1 receptor to PI3K–Akt signaling. S6K1 (activated by mTORC1) phosphorylates and destabilizes IRS1/2, creating a negative feedback loop. Rapamycin blocks mTORC1/S6K1, relieving IRS1 inhibition and allowing paradoxical Akt re-activation — a critical consideration in the clinical use of rapalogs.
MRPS17 0 Mitochondrial ribosomal protein S17, upregulated in lung adenocarcinoma where it activates PI3K-AKT-mTOR signalling.
PFKFB3 0 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, a rate-limiting glycolytic regulator controlled downstream of mTORC2.
PXR (NR1I2) 0 Pregnane X receptor, a xenobiotic-sensing nuclear receptor whose activation drives liver growth via the AKT-mTOR pathway.
SGK1 0 Serum- and glucocorticoid-regulated kinase 1; a second major AGC kinase phosphorylated and activated by mTORC2 at its hydrophobic motif. Controls ion transport, cell survival, and glucose metabolism. mTORC2→SGK1 signaling is a key output branch of mTORC2 parallel to the mTORC2→Akt axis.
SIN1 / MAPKAP1 0 Essential structural subunit of mTORC2 (stress-activated protein kinase-interacting protein 1). Required for mTORC2 assembly and integrity; controls the substrate specificity of mTORC2 toward Akt and other AGC kinases. Prolonged rapamycin treatment can disrupt SIN1-containing mTORC2, explaining chronic-rapamycin-induced impairment of Akt signaling.
SLC7A5 (LAT1) 0 Large neutral amino acid transporter 1, which imports leucine and is a key upstream input into mTORC1 nutrient sensing.
SREBP1 / SREBP2 0 Sterol regulatory element-binding proteins 1 and 2; master transcription factors for de novo lipid and cholesterol biosynthesis. mTORC1 promotes SREBP nuclear entry (via Lipin-1 and S6K1), linking nutrient sensing to the lipogenic program. SREBP1/2 are thus a major downstream metabolic output of mTORC1 alongside protein synthesis and autophagy suppression.
TET1 0 Ten-eleven translocation methylcytosine dioxygenase 1, an epigenetic eraser that drives DNA demethylation of target promoters.

Complexes & pathways 11

mTORC1 80 mTOR Complex 1; regulates protein synthesis, autophagy, and growth in response to nutrients and growth factors.
mTORC2 14 mTOR Complex 2; phosphorylates Akt/PKB, affects cell survival and glucose metabolism.
Ragulator 3 Lysosome-anchored scaffold that recruits the Rag GTPases and positions mTORC1 on the lysosomal surface for activation.
GATOR1 2 Negative regulator of the Rag GTPases (a GAP); switches mTORC1 OFF when amino acids are scarce. Tumor suppressor - mutated in some cancers.
GATOR2 2 Positive arm that inhibits GATOR1; the target through which amino acid sensors (Sestrin2, CASTOR1) relay their signal to mTORC1.
Growth hormone / IGF-1 axis 2 Upstream growth-signaling axis; reduced activity (as in Ames dwarf mice) is one of the most robust lifespan-extending interventions known in mammals, acting upstream of PI3K/Akt/mTOR.
cGAS-STING pathway 1 An innate immune sensing pathway triggered by cytosolic DNA; drives inflammatory senescence signaling and is activated downstream of mTOR dysfunction in aging immune cells.
Integrated stress response 1 Conserved response to unfolded protein, amino-acid and other stresses. Reaches mTORC1 by routes independent of both TSC and AMPK.
KICSTOR 0 A lysosomal scaffold complex (composed of KAPTIN, ITFG2, C12orf66, and SZT2) that recruits GATOR1 to the lysosomal surface. Required for amino-acid-deprivation-dependent suppression of mTORC1; without KICSTOR, GATOR1 cannot reach the Rag GTPases and mTORC1 remains inappropriately active during starvation.
NF-κB 0 Master pro-inflammatory transcription factor complex that cross-talks extensively with PI3K/AKT/mTOR signalling.
NLRP3 0 Inflammasome sensor driving IL-1β-mediated inflammation, regulated in part by mTOR-dependent immunometabolism.

Drugs 23

Rapamycin 39 Sirolimus; mTORC1 inhibitor (and, with chronic dosing, mTORC2 too); immunosuppressant; extends lifespan in mice.
Everolimus 14 Rapamycin analog (RAD001); used in oncology and tested for immune function in older adults.
Metformin 3 Antidiabetic biguanide; activates AMPK (ZHO2001) and inhibits mTORC1. How much of its action actually runs through AMPK is disputed: metformin still suppresses hepatic gluconeogenesis in AMPK-null and LKB1-null mouse liver (FOR2010) and still inhibits mTORC1 in AMPK-null cells, via the Rag GTPases (KAL2010). Frequently discussed as a geroprotector alongside rapamycin.
Resveratrol 3 Plant polyphenol popularized as a sirtuin activator and 'calorie-restriction mimetic'; failed to extend lifespan in ITP mouse studies and showed no metabolic benefit in a human RCT.
Acarbose 2 Alpha-glucosidase inhibitor (diabetes drug) that slows carbohydrate absorption; found by the ITP to extend mouse lifespan, especially in males.
RTB101 2 An oral ATP-competitive mTOR inhibitor (formerly BEZ235) tested for boosting immune function in the elderly; improved antiviral gene expression but failed its phase 3 clinical endpoint.
Astragaloside IV 1 Bioactive saponin from Astragalus membranaceus that inhibits mTOR to activate TFEB-mediated autophagy, protecting against tacrolimus-induced nephrotoxicity.
Curcumin 1 Turmeric-derived polyphenol widely marketed for anti-aging effects; showed no lifespan effect in ITP testing.
Green tea extract 1 Polyphenol-rich supplement tested by the ITP for lifespan effects; no significant effect found overall.
MCT oil 1 Medium-chain triglyceride oil; tested by the ITP as a metabolic/longevity intervention with no significant lifespan effect.
Melittin 1 The main bioactive component of bee venom; suppresses PI3K/Akt/mTOR pathway and activates autophagy, showing anti-inflammatory effects in psoriasis models.
Oxaloacetic acid 1 Metabolic intermediate marketed as a longevity supplement; no lifespan effect found in ITP testing.
PP242 1 An ATP-competitive mTOR kinase inhibitor (a 'TORKinib'); like Torin1, inhibits both mTORC1 and mTORC2 and blocks outputs that rapamycin leaves intact.
Simvastatin 1 Cholesterol-lowering statin; tested as a candidate longevity drug in the same ITP cohort as rapamycin but showed no lifespan effect.
Temsirolimus 1 Intravenous rapamycin ester (CCI-779); mTOR inhibitor approved for advanced renal cell carcinoma.
Torin1 1 ATP-competitive ('active-site') mTOR inhibitor. Unlike rapamycin, it blocks the kinase active site directly and so fully inhibits BOTH complexes - the tool that revealed rapamycin-resistant functions of mTORC1.
Urolithin A 1 Gut microbiome-derived polyphenol metabolite that activates mitophagy via the AMPK-mTOR axis, with cardioprotective effects in heart failure models.
Cisplatin 0 Platinum-based chemotherapeutic whose tolerance is modulated by mTOR-dependent cytoprotective autophagy.
Corilagin 0 Natural ellagitannin with anti-inflammatory activity that inhibits PI3K/AKT/mTOR and NF-κB signalling and restores autophagy.
Dihydromyricetin 0 Flavonoid from Ampelopsis grossedentata reported to reduce fibrosis with accompanying suppression of PI3K/AKT/mTOR signalling.
Forsythoside A 0 Phenylethanoid glycoside from Forsythiae Fructus that binds ASCL1 and blocks a downstream CCNB1/mTOR axis.
Pungenin 0 Phenolic glucoside from Picea wilsonii that promotes hair regrowth via transcriptional regulation of the PI3K/AKT/FoxO/mTOR axis.
Salvianolic acid B 0 Polyphenol from Salvia miltiorrhiza that engages AKT1 and the AKT/mTOR/HIF-1α axis to promote angiogenesis and repair.

Diseases 14

Tuberous sclerosis complex 5 Genetic disorder from TSC1/TSC2 loss causing constitutive mTOR activation and benign tumors in brain, kidney, and elsewhere. Everolimus shrinks these tumors (EXIST trials) - the clearest randomised human evidence that blocking mTOR helps a human disease driven by mTOR overactivation.
Alzheimer's disease 3 Neurodegenerative disease marked by amyloid-beta plaques and tau tangles. mTOR overactivation blocks the autophagy that would clear these toxic proteins; rapamycin restores clearance in mouse models.
Breast cancer 3 Hormone-receptor-positive advanced breast cancer becomes resistant to endocrine therapy partly by activating mTOR; adding the rapalog everolimus re-sensitizes it (BOLERO-2).
Renal cell carcinoma (RCC) 3 Cancer of the kidney; target indication for everolimus treatment in clinical practice.
Huntington's disease 2 Neurodegenerative disease caused by a toxic polyglutamine-expanded protein; cleared via mTOR-inhibition-induced autophagy in animal models.
Lymphangioleiomyomatosis 2 LAM - a rare progressive cystic lung disease in women driven by inappropriate mTOR activation; sirolimus stabilizes lung function (MILES trial).
Pancreatic neuroendocrine tumor 1 Pancreatic neuroendocrine tumor - a cancer where mTOR drives growth; everolimus more than doubled progression-free survival (RADIANT-3), an FDA-approved indication.
Prostate cancer 1 Cancer in which oncogenic mTOR signaling reprograms the cell's translation to drive proliferation, invasion and metastasis.
Atrial fibrillation 0 The most common age-related cardiac arrhythmia, driven by atrial electrical and structural remodelling.
Autoimmune cytopenia 0 Immune-mediated destruction of blood cell lineages (including Evans syndrome and pure red cell aplasia) in which sirolimus is used as a T-cell-directed therapy.
Lung cancer (NSCLC/LUAD) 0 Non-small cell lung cancer including lung adenocarcinoma, in which PI3K-AKT-mTOR and mTORC2 signalling are frequently dysregulated.
Osteoarthritis 0 Age-related degenerative joint disease characterised by cartilage matrix loss, inflammation and impaired chondrocyte autophagy.
Parkinson's disease 0 Neurodegenerative disease marked by loss of dopaminergic neurons and accumulation of misfolded alpha-synuclein (Lewy bodies). mTORC1 hyperactivity suppresses the autophagy that would clear alpha-synuclein aggregates; rapamycin enhances their autophagic clearance in animal models. Relevant to gap H8 (brain-penetrant mTOR inhibition for aggregate clearance).
Spinal cord injury 0 Traumatic CNS injury in which AKT/mTOR-driven angiogenesis and neuronal survival are targets for functional recovery.

Conditions 3

Energy & cellular stress 4 Falling ATP, glucose withdrawal and a range of other insults. They converge on mTORC1 through two routes: AMPK, and physical relocation of the TSC complex to the lysosome.
Hypoxia 1 Low oxygen. Acts on mTORC1 transcriptionally through REDD1 rather than through AMPK, so it is slower to engage and slower to release.
Lung transplant 0 Clinical setting in which mTOR inhibitors are used as antiproliferative, calcineurin-sparing immunosuppression, notably against chronic lung allograft dysfunction.

Processes 15

Autophagy 18 Cellular recycling process suppressed by mTORC1 and activated upon its inhibition; linked to longevity.
Protein synthesis 6 Cap-dependent translation - the main output mTORC1 exists to control, and the step where a signalling decision becomes physical growth.
Tumor growth 5 The shared endpoint of the pathway's oncogenic lesions, and the outcome every mTOR inhibitor trial in this Atlas was actually measuring.
Lipid synthesis 4 De novo synthesis of fatty acids and cholesterol via SREBP. A growing cell needs membrane as much as it needs protein; both mTOR complexes feed this.
Nucleotide synthesis 4 De novo purine and pyrimidine production. mTORC1 matches supply to demand here, which is why proliferating cells are so dependent on it.
Actin cytoskeleton 3 Cell shape and motility machinery. The first function ever attributed to mTORC2 - and noticed precisely because rapamycin failed to block it.
Cellular senescence 3 State in which a cell permanently stops dividing but stays alive, secreting inflammatory signals (the SASP). Senescent cells accumulate with age and drive age-related disease. mTOR both promotes the senescent state and powers its inflammatory secretions.
Muscle growth 3 mTORC1-dependent process of skeletal muscle fiber enlargement (hypertrophy); driven by growth factors and exercise, blocked by rapamycin.
5'TOP mRNA 2 Class of mRNAs with a 5' terminal oligopyrimidine tract encoding ribosomal proteins and translation factors; their translation is a canonical output of mTORC1 signaling.
Mitochondrial biogenesis 1 Production of new mitochondria and their oxidative machinery. mTORC1 drives it via a YY1-PGC-1alpha transcriptional program, linking growth signaling to energy production.
Mitophagy 1 Selective autophagic degradation of damaged or dysfunctional mitochondria; regulated by the AMPK-mTOR-ULK1 axis and implicated in cardiac protection, neurodegeneration, and aging.
T cell differentiation 1 Process by which immune T cells commit to effector versus regulatory fates; directly controlled by mTOR complex activity.
Ferroptosis 0 Iron-dependent, lipid-peroxidation-driven regulated cell death that is modulated by mTOR signalling and autophagy.
Macrophage polarization 0 The M1/M2 phenotypic switch in macrophages, an immunometabolic decision governed substantially by PI3K/AKT/mTOR signalling.
Placental nutrient sensing 0 Placental mTORC1-dependent regulation of amino acid transport and mitochondrial respiration that sets fetal growth trajectory.

Outcomes 7

Longevity 37 Lifespan extension; the key outcome tracked across mTOR-targeting interventions.
Immune function 5 Function of the immune system, especially vaccine response; improved by low-dose everolimus in older adults.
Insulin resistance 4 Metabolic side effect of chronic mTOR inhibition. In mice, mTORC2 disruption is a major contributor (LAM2012). In humans the relative contributions are not resolved: mTORC2 loss, S6K1-IRS-1 feedback relief (HAR2004, SHA2004) and direct beta-cell effects are all plausible, and no study has apportioned them.
Cardiac aging 1 Age-related decline in heart function (hypertrophy, stiffening, reduced contractility). Late-life rapamycin partially reverses it in mice.
Cognition 1 Learning, memory and related brain function. mTOR inhibition can enhance cognition in young mice and blunt age-related cognitive decline.
Kidney transplant 1 Original and still-standard clinical use of rapamycin (as sirolimus), preventing organ rejection by suppressing T cell activation.
Skin aging 1 Visible and molecular aging of skin (photodamage, dermal thinning, senescence markers like p16). Topical rapamycin reduced these markers in a human trial.

Interventions 3

Caloric restriction 4 Reduced caloric intake without malnutrition; associated with lifespan extension across species.
Leucine/BCAA restriction 1 Restriction of branched-chain amino acids (leucine, isoleucine, valine); modulates mTORC1 via the Sestrin2 sensor.
Macronutrient ratio 1 Ratio of protein:carbohydrate:fat in the diet; affects mTOR activation independently of total caloric intake.

Nutrients & metabolites 6

Arginine 5 Essential amino acid sensed by two separate routes: cytosolic arginine binds CASTOR1, and lysosomal arginine is read by the transporter-like protein SLC38A9.
Leucine 5 Branched-chain essential amino acid and the best-characterised nutrient input to mTORC1. Free leucine binds Sestrin2, releasing the GATOR2 brake; a competing model has leucyl-tRNA synthetase as the sensor instead.
Glutamine 2 Most abundant free amino acid; activates mTORC1 partly through glutaminolysis and, in some settings, through a Rag-independent Arf1 route - one of the clearest examples that 'amino acid sensing' is not a single mechanism.
Kynurenic acid 1 A tryptophan metabolite produced by tumor microbiota (e.g. Fusobacterium nucleatum); activates the ITGA2-mTOR-CTSV axis to suppress CD8+ T cell function and drive immunotherapy resistance.
S-adenosylmethionine (SAM) 1 Universal methyl donor whose level reports methionine availability. SAM binds SAMTOR, which otherwise inhibits mTORC1 through the GATOR1-KICSTOR complex.
Bisphenol A 0 Ubiquitous environmental plasticiser that disrupts intestinal barrier function and mitochondrial metabolism, perturbing AMPK-mTOR signalling.

Organelles 1

Lysosome 4 The organelle on whose surface mTORC1 is activated. Nutrient signals converge here: mTORC1 must be physically recruited to the lysosomal membrane before Rheb can switch it on.