Sirolimus; mTORC1 inhibitor (and, with chronic dosing, mTORC2 too); immunosuppressant; extends lifespan in mice.
| Study | Year | Tier | Finding |
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| 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; |
| 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 |
| 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 |
| 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 |
| 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 |
| DRU2009 | 2009 | B | Rapamycin given before resistance exercise completely blocked the normal post-exercise increase in human muscle protein synthesis.
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| KAH2000 | 2000 | B | The trial that established rapamycin (sirolimus) as an immunosuppressant in kidney transplant patients - its original, still-standard clinical use.
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| 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.
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| 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.
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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 |
| 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 |
| 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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| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| LAM2012 | 2012 | D | Chronic rapamycin disrupts mTORC2 as well, causing insulin resistance; lifespan extension can be uncoupled from this side effect.
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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 |
| 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 |
| 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 |
| SAR2006 | 2006 | D | 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 mechanisti |
| 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.
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| 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.
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| VEZ1975 | 1975 | D | 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.
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| 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 |