Gene/Protein · 58 studies in the Atlas · also known as MTOR, mechanistic target of rapamycin, mammalian target of rapamycin, FRAP1, TOR, dTOR
Serine/threonine kinase; central regulator of cell growth and metabolism; direct target of rapamycin.
| Study | Year | Tier | Finding |
|---|
| LEE2024 | 2024 | A | 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; |
| MOE2025 | 2025 | B | 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 exactly |
| 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= |
| WAG2014 | 2014 | B | An activating MTOR mutation underlies an extraordinary clinical response to rapalog therapy.
|
| 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 |
| 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 |
| KRU2010 | 2010 | B | In patients whose TSC1/TSC2 mutations cause brain tumors, everolimus shrank tumor volume by 30%+ in three-quarters of patients.
|
| BIS2008 | 2008 | B | Sirolimus shrinks renal angiomyolipomas in tuberous sclerosis / lymphangioleiomyomatosis.
|
| HUD2007 | 2007 | B | 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 |
| KAH2000 | 2000 | B | The trial that established rapamycin (sirolimus) as an immunosuppressant in kidney transplant patients - its original, still-standard clinical use.
|
| LIS2026 | 2026 | C | Notoginsenoside R1 alleviates acetaminophen-induced acute liver injury by activating protective autophagy through MAPK/mTOR pathway modulation, reducing hepatocyte death and oxidative damage.
|
| LV2026 | 2026 | C | Age-driven loss of Lamtor5, a key lysosomal mTOR activation complex subunit, causes macrophage immunosenescence and systemic aging by unleashing cGAS-STING paracrine inflammation; Lamtor5 restoration |
| SONH2026 | 2026 | C | 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 l |
| VER2026 | 2026 | C | 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 worsen |
| ZHU2026 | 2026 | C | LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, estab |
| URF2017 | 2017 | C | A short 10-week course of low-dose rapamycin improved heart function measures in healthy pet dogs with no clinical side effects.
|
| BIT2016 | 2016 | C | Just 3 months of rapamycin late in life increased subsequent life expectancy by up to 60% - evidence that transient, not lifelong, dosing can capture the benefit.
|
| FOK2014 | 2014 | C | Rapamycin-fed mice show extended lifespan with major changes in the liver transcriptome.
|
| MIL2014 | 2014 | C | Rapamycin's lifespan extension in mice is dose-dependent and greater in females.
|
| 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 |
| NEF2013 | 2013 | C | Rapamycin extends murine lifespan but has only limited effects on classic aging phenotypes.
|
| 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 |
| MIL2011 | 2011 | C | 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 co |
| LIX2010 | 2010 | C | Ketamine's rapid antidepressant action requires mTOR-dependent synaptogenesis in prefrontal cortex.
|
| ARA2009 | 2009 | C | mTOR is a key regulator of memory CD8 T-cell differentiation; rapamycin enhances memory responses.
|
| CAS2009 | 2009 | C | Wnt-induced mTOR activation drives epidermal stem-cell senescence; rapamycin rescues it.
|
| HAR2009 | 2009 | C | Rapamycin fed from 600 days of age extended median lifespan by 9-14% in both sexes.
|
| KAE2005 | 2005 | C | A systematic screen of 564 yeast gene deletions found TOR and Sch9 pathway genes as the strongest lifespan-extending hits.
|
| VEL2003 | 2003 | C | 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.
|
| BO2026 | 2026 | D | Gambogic acid exerts anti-tumor activity in lung cancer cells primarily by targeting and inhibiting mTOR signaling, demonstrated through integrated computational docking and in vitro experimental vali |
| GAO2026 | 2026 | D | Astragaloside IV protects against tacrolimus-induced nephrotoxicity by inhibiting mTOR to activate TFEB and restore autophagy, identifying the mTOR-TFEB-GADD45alpha axis as a calcineurin-independent t |
| JIB2026 | 2026 | D | Rapamycin fails to protect spermatogonial stem cells from cisplatin-induced damage in vitro, indicating sex-specific or context-specific limits to rapamycin's cytoprotective role and suggesting male f |
| LI2026 | 2026 | D | 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. |
| HAN2025 | 2025 | D | 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 |
| BOU2020 | 2020 | D | 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) -- the |
| 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, |
| MOS2018 | 2018 | D | Review of mTOR and cellular metabolism as mutual determinants in cancer.
|
| SAB2017 | 2017 | D | Sabatini's 25-year synthesis linking nutrient sensing to growth through mTOR.
|
| SAX2017 | 2017 | D | Comprehensive synthesis of mTORC1/mTORC2 signaling, growth regulation, metabolism, and disease relevance.
|
| GUR2016 | 2016 | D | Review of how mTOR signalling confers resistance to targeted cancer therapies.
|
| 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 |
| ROD2016 | 2016 | D | RapaLink-1, a third-generation bivalent inhibitor, overcomes mTOR resistance mutations.
|
| GRA2014 | 2014 | D | A spectrum of cancer-associated MTOR mutations are hyperactivating and predict rapamycin sensitivity.
|
| 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 |
| YAN2013 | 2013 | D | 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 subs |
| POW2011 | 2011 | D | Review of mTOR as an integrator of immune-cell metabolism and differentiation.
|
| 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.
|
| 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 |
| GUE2007 | 2007 | D | Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology.
|
| BLA2006 | 2006 | D | Proposes the 'hyperfunction theory' of aging: TOR signaling, useful in youth, stays switched on into old age and becomes actively damaging.
|
| SAR2004 | 2004 | D | 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 tha |
| 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 |
| 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 |
| 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 |
| CHO1996 | 1996 | D | 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 |
| SAB1994 | 1994 | D | Discovery of the protein RAFT1 (today's mTOR) as the direct target of the FKBP12-rapamycin complex; founding paper of the entire mTOR field.
|
| HEI1991 | 1991 | D | 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.
|