Lifespan extension; the key outcome tracked across mTOR-targeting interventions.
| 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 |
| 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 |
| BAN2014 | 2014 | B | Diabetic patients started on metformin had longer median survival than matched non-diabetic controls without the drug.
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| MAT2017 | 2017 | C | Direct comparison of two long-term primate CR studies (NIA, Wisconsin) confirms health benefits; survival effect depended on study design.
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| 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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| HAR2014 | 2014 | C | Beyond rapamycin, the same ITP program found acarbose extended male median lifespan by 22% - proof the registry finds real positive hits too, not only negative results.
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| 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 |
| PYO2013 | 2013 | C | Mice engineered with extra copies of the autophagy gene Atg5 lived 17% longer and were leaner and more insulin-sensitive.
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| 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, |
| STR2012 | 2012 | C | 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 r |
| 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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| 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 |
| KAE2005 | 2005 | C | A systematic screen of 564 yeast gene deletions found TOR and Sch9 pathway genes as the strongest lifespan-extending hits.
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| KAP2004 | 2004 | C | Genetically reducing TOR pathway activity extends fruit fly lifespan, overlapping with dietary restriction effects.
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| MEL2003 | 2003 | C | Worms lacking the autophagy gene bec-1 lost the lifespan-extending benefit of reduced insulin-like signaling - autophagy is mechanistically required for longevity, not just correlated.
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| 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.
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| BRO1996 | 1996 | C | Mice with growth hormone deficiency lived substantially longer than normal littermates - founding observation linking reduced growth-signaling to mammalian longevity.
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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 |
| 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 |
| 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, |
| 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 |
| 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 |
| 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 |
| 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 |
| 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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| NCT05835999 | | — | 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 insuli |