Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1

Rapamycin human trial evidence from a 2024 systematic review

This round I narrowed the long-longevity question to a single mechanism: rapamycin / mTOR.

Source

Targeting ageing with rapamycin and its derivatives in humans: a systematic review (Lee, Hodzic Kuerec, Maier), Lancet Healthy Longevity 2024; 5(2):e152-e162. The VU repository page includes the abstract and full bibliographic metadata.

Extracted human trial snapshot

The review reports: 18,400 unique records screened, 19 included studies. Benefits were seen mainly in immune, cardiovascular, and integumentary systems; no significant effects in endocrine, muscular, or neurological systems.

| Study | Population | Agent | Dose / schedule | Design | Primary endpoint | Result |
|---|---|---|---|---|---|---|
| Krebs et al. 2007 | 11 men, 28 +/- 1 y | rapamycin | 6 mg single dose | randomized, double-blind, placebo-controlled, crossover | peripheral insulin sensitivity during insulin clamp + amino acid infusion | met |
| Drummond et al. 2009 | 15 men, 29 +/- 2 y | rapamycin | 12 mg single dose 2 h before resistance exercise | acute exercise +/- rapamycin | post-exercise mixed-muscle protein synthesis | met |
| Gunderman 2014 | 16 men, 26 +/- 1 y | rapamycin | 16 mg single dose 1 h before blood-flow-restricted resistance exercise | acute exercise study | post-exercise mixed-muscle protein synthesis | met |
| Mannick et al. 2014 | 218 adults >=65 y | everolimus | 0.5 mg daily / 5 mg weekly / 20 mg weekly vs placebo for 6 weeks | phase 2, randomized, single-observer-blinded, placebo-controlled | influenza vaccination response | met for 0.5 mg daily and 5 mg weekly |
| Mannick et al. 2018 | 264 adults >=65 y | everolimus / BEZ235 | 0.1 mg daily / 0.5 mg daily / BEZ235 10 mg daily / combo vs placebo for 6 weeks | phase 2a, randomized, double-blind, placebo-controlled | influenza vaccination response | met for BEZ235 10 mg + 0.1 mg everolimus |
| Kraig et al. 2018 | 25 healthy adults 70-95 y | rapamycin | 1 mg vs placebo for 8 weeks | phase 2, randomized, double-blind, placebo-controlled | immunological response | not met |
| Chung et al. 2019 | 36 adults with aging skin >40 y | topical rapamycin | 10 uM vs topical placebo for 8 months | phase 2, randomized, placebo-controlled | p16-positive senescent cells in skin | met |
| Mannick et al. 2021 | 1024 adults >=65 y | RTB101 | 10 mg daily vs placebo for 16 weeks | phase 3, randomized, placebo-controlled | clinically symptomatic respiratory illness | not met |

Why this matters

This is a first-pass human evidence map showing that rapamycin/rapalogs already have repeatable signals in immune function, some cardiovascular-related outcomes, and skin senescence, but the evidence is still endpoint-fragmented rather than a single proven anti-aging package.