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 as pre-registered. Secondary endpoints were more promising: women on the 10mg/week dose had significant improvements in lean muscle mass and self-reported pain. A textbook example of why the pre-registered primary endpoint, not the most exciting secondary finding, is what should drive the headline conclusion.
| Evidence tier | B Direct human evidence |
| Study type | 2 - Human Clinical Trial |
| Model system | Humans, RCT, ages 50-85 (n=114 completed) |
| Journal | Aging (Albany NY) |
| Year | 2025 |
| Peer reviewed | Yes |
| Source | DOI 10.18632/aging.206235 · PMID 40188830 · Free full text (PMC12074816) |
This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly. The primary outcome measure was visceral adiposity (by DXA scan), secondary outcomes were blood biomarkers, and lean tissue and bone mineral content (by DXA scan). Established surveys were utilized to evaluate health and well-being. Safety was assessed through adverse events and blood biomarker monitoring. Adverse and serious adverse events were similar across all groups. Visceral adiposity did not change significantly (η= 0.001,= 0.942), and changes in blood biomarkers remained within normal ranges. Lean tissue mass (η= 0.202,= 0.013) and self-reported pain (η= 0.168,= 0.015) improved significantly for women using 10 mg rapamycin. Self-reported emotional well-being (η= 0.108,= 0.023) and general health (η= 0.166,= 0.004) also improved for those using 5 mg rapamycin. No other significant effects were observed. Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women. Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy.
| Intervention | Intermittent low-dose rapamycin (5/10 mg weekly, 48 wk) |
| Target | mTOR |
| Model | Human – RCT (PEARL, ages 50-85, n=114 completed) |
| Effect | Intermittent low-dose rapamycin was safe over 1 year; some healthspan gains (e.g. lean tissue in women at 10 mg) |