Pathway/Complex · 73 studies in the Atlas · also known as TORC1, mTOR complex 1, mTOR complex-1
mTOR Complex 1; regulates protein synthesis, autophagy, and growth in response to nutrients and growth factors.
| Study | Year | Tier | Finding |
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| GIL2026 | 2026 | B | Low-dose rapamycin in ME/CFS patients reduced fatigue symptoms, modulated purine biosynthesis via IMP dehydrogenase inhibition, reduced microglial inflammatory responses, and improved mitochondrial en |
| MAR2026 | 2026 | B | 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, with |
| SCH2025 | 2025 | B | First-in-human trial of a bi-steric mTORC1-selective inhibitor. Treatment-related hyperglycemia was low (4%) and not dose-limiting -- direct clinical confirmation that sparing mTORC2 avoids the metabo |
| MAN2021 | 2021 | B | 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= |
| CHU2019 | 2019 | B | 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 V |
| KRA2018 | 2018 | B | 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 r |
| MAN2018 | 2018 | B | The strongest human evidence that mTOR inhibition can rejuvenate a specific function of aging - immunity. In 264 elderly people, a low-dose combination that selectively hits TORC1 significantly reduce |
| BIS2013 | 2013 | B | 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 |
| FRA2013 | 2013 | B | 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 ca |
| BAS2012 | 2012 | B | A phase 3 RCT (n=724) proving mTOR matters in a common cancer. When hormone-therapy stops working in breast cancer, it's partly because mTOR switches on. Adding everolimus more than doubled progressio |
| MCC2011 | 2011 | B | A landmark RCT (n=89) - the first to prove rapamycin (sirolimus) treats a human lung disease. In LAM, lung function normally declines relentlessly; sirolimus STOPPED that decline while patients took i |
| YAO2011 | 2011 | B | 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 pro |
| DRU2009 | 2009 | B | Rapamycin given before resistance exercise completely blocked the normal post-exercise increase in human muscle protein synthesis.
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| DEN2026 | 2026 | C | 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 in |
| YAN2026 | 2026 | C | SLC15A3-mediated dipeptide import sustains mTORC1 activation in B cell lymphomas, enabling resistance to antimetabolite chemotherapy; inhibiting SLC15A3 or mTORC1 restores drug sensitivity.
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| MEN2023 | 2023 | C | 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-inhib |
| SOL2014 | 2014 | C | Lifespan and cardiometabolic health were determined not by caloric intake but by the protein:carbohydrate ratio; low protein ratio suppressed hepatic mTOR.
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| FLY2013 | 2013 | C | Striking proof that mTOR inhibition doesn't just SLOW aging - it can partly REVERSE it. Giving rapamycin to already-old (24-month) mice for 3 months improved aged heart function, reversing age-related |
| HAL2012 | 2012 | C | 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, |
| WIL2012 | 2012 | C | 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), i |
| BJE2010 | 2010 | C | Feeding rapamycin extended fly lifespan through autophagy and reduced translation, and worked even in flies already on a lifespan-maximizing diet.
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| CAC2010 | 2010 | C | 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- |
| SPI2010 | 2010 | C | 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 wit |
| HAR2009 | 2009 | C | Rapamycin fed from 600 days of age extended median lifespan by 9-14% in both sexes.
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| SEL2009 | 2009 | C | Deleting S6K1 (a direct mTORC1 effector) extended lifespan and protected against age-related bone, immune, and motor decline in mice.
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| ZID2009 | 2009 | C | Connected the dots between diet, mTOR, and lifespan. Dietary restriction lowers mTOR activity, which frees up 4E-BP - and here 4E-BP was shown to be REQUIRED for the lifespan boost, working by selecti |
| CHE2008 | 2008 | C | 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 abili |
| KAP2004 | 2004 | C | Genetically reducing TOR pathway activity extends fruit fly lifespan, overlapping with dietary restriction effects.
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| RAV2004 | 2004 | C | Rapamycin-induced autophagy cleared toxic clumped proteins and improved symptoms in fly and mouse models of Huntington's disease.
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| PIR2026 | 2026 | D | 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 c |
| HE2025 | 2025 | D | 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, n |
| JOS2024 | 2024 | D | 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 |
| LIU2020 | 2020 | D | 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, |
| GU2017 | 2017 | D | 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 |
| HOW2017 | 2017 | D | 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 |
| SAX2017 | 2017 | D | Comprehensive synthesis of mTORC1/mTORC2 signaling, growth regulation, metabolism, and disease relevance.
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| CHA2016 | 2016 | D | 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 th |
| KEN2016 | 2016 | D | 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 metaboli |
| LAB2015 | 2015 | D | 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 cytoki |
| SAX2015 | 2015 | D | Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor.
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| BAR2013 | 2013 | D | 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 |
| JOH2013 | 2013 | D | The definitive 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 disea |
| HSI2012 | 2012 | D | 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 inh |
| LAP2012 | 2012 | D | 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 deregu |
| MAR2012 | 2012 | D | Pinned down the direct mTORC1-TFEB link: 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 |
| THO2012 | 2012 | D | Used ribosome profiling with the complete inhibitor Torin1 to settle a long debate: mTORC1's translational control runs almost entirely through the 4E-BP family acting on a specific class of mRNAs (TO |
| KIM2011 | 2011 | D | 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 |
| SET2011 | 2011 | D | Established TFEB as the single master switch that coordinates the WHOLE recycling program - it turns on both autophagosome and lysosome genes at once during starvation. This is the transcription facto |
| ZON2011 | 2011 | D | 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 c |
| FON2010 | 2010 | D | The landmark synthesis showing that eating less (dietary restriction) and dialing down nutrient-sensing pathways - mTOR and growth hormone/IGF-1 - extend healthy lifespan by the SAME conserved mechani |
| SAN2010 | 2010 | D | 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 live |
| DEL2009 | 2009 | D | 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.
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| DEM2009 | 2009 | D | 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 |
| FEL2009 | 2009 | D | 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 |
| HOS2009 | 2009 | D | 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 |
| PET2009 | 2009 | D | 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 |
| THO2009 | 2009 | D | 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 phosp |
| GWI2008 | 2008 | D | 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 'met |
| SAN2008 | 2008 | D | 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.
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| CUN2007 | 2007 | D | 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 progr |
| GUE2007 | 2007 | D | Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology.
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| SAN2007 | 2007 | D | 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 |
| BLA2006 | 2006 | D | Proposes the 'hyperfunction theory' of aging: TOR signaling, useful in youth, stays switched on into old age and becomes actively damaging.
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| GUE2006 | 2006 | D | The definitive 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 a |
| INO2003 | 2003 | D | 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 |
| KIM2003 | 2003 | D | 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 e |
| TEE2003 | 2003 | D | TSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and directly activates mTORC1.
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| HARA2002 | 2002 | D | 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 - confi |
| INO2002 | 2002 | D | 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.
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| KIM2002 | 2002 | D | 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 th |
| ROM2001 | 2001 | D | Shows IGF-1 drives muscle fiber hypertrophy specifically through the Akt-mTOR pathway, establishing mTORC1 as a central node for muscle growth signaling.
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| MUT2026 | 2026 | — | 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 |
| TAN2024 | 2024 | — | In mice engineered to overexpress a phosphomimetic tau variant, one week of rapamycin reversed tau-driven mitochondrial dysfunction and rescued cognitive performance in the Morris water maze - extends |