Rapamycin (sirolimus)
DERapamycin (Sirolimus)
Reviewed by Maurice Lichtenberg
Rapamycin (sirolimus) is a macrolide mTORC1 inhibitor approved as an immunosuppressant to prevent kidney transplant rejection and to treat lymphangioleiomyomatosis. By inhibiting mTORC1, it slows protein synthesis, enhances autophagy, and extends lifespan in yeast, worms, flies, and mice across multiple labs. Off-label use for human longevity remains investigational; clinical trials are evaluating intermittent low-dose protocols, but efficacy and long-term safety in healthy adults are unproven. The PEARL trial (Moel et al., Aging-US April 2025) reported safety similar across groups; the primary efficacy endpoint of visceral adipose tissue change was not met, but secondary outcomes showed dose-dependent improvements in lean mass and pain in women on 10 mg/week.
Sources
- Harrison DE, Strong R, Sharp ZD et al.. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. *Nature*doi:10.1038/nature08221
- Moel M, Harinath G, Lee V, Nyquist A, Morgan SL, Isman A, Zalzala S. (2025). The PEARL trial: a randomized, double-blind, placebo-controlled trial of rapamycin in healthy aging adults. *Aging (Albany NY)*doi:10.18632/aging.206235