Rapamycin (sirolimus) is an mTOR inhibitor with the most reproducible lifespan-extending effects across species in preclinical research. Now being explored as a human longevity intervention using low intermittent dosing. Requires physician supervision and periodic lab monitoring.
Rapamycin was discovered in a soil sample from Easter Island (Rapa Nui) in the 1970s and has been used since 1999 as an immunosuppressant in organ transplant patients at daily doses of 2–5 mg. At these high, daily doses, it suppresses the immune system to prevent organ rejection.
The longevity application uses a fundamentally different dosing approach: low doses (1–6 mg) taken once per week, not daily. At these intermittent low doses, the drug's effects on the mTOR pathway are thought to differ meaningfully from continuous high-dose immunosuppression.
Animal studies: Rapamycin has extended lifespan in mice by 9–26% across multiple independent labs and mouse strains — a level of reproducibility unusual in aging research. It has also extended lifespan in yeast, worms, and flies. It is the most consistent lifespan-extending drug studied to date.
Human studies: A 2014 study by Mannick et al. showed that low-dose rapamycin analogs improved immune function in elderly volunteers (the opposite of the transplant-dose effect) and improved response to influenza vaccination. The PEARL trial and other ongoing studies are investigating rapamycin's effects on aging biomarkers, skin aging, and age-related diseases.
What we don't know: There are no completed large-scale randomized human longevity trials. Current off-label use is based on compelling preclinical evidence plus emerging human data.
Typical longevity protocol: 1–6 mg orally once per week. Some physicians use 3–6 mg every 1–2 weeks with periodic "drug holidays." Your physician will determine the appropriate dose based on health status, labs, tolerance, and goals. This is not the daily high-dose immunosuppressive protocol used in transplant medicine.
At low weekly doses: Mouth sores (canker-like, most common and dose-dependent), dose-related lipid changes (elevated triglycerides/cholesterol), and potentially impaired wound healing.
At high daily doses (transplant-level, NOT what we prescribe): immunosuppression, increased infection risk, metabolic effects. Not generally seen at low intermittent doses.
Contraindications: active infection, immunocompromise, pending surgery (impairs wound healing), pregnancy or breastfeeding. Patients with pre-existing hyperlipidemia should discuss risks.
Medical disclaimer: Off-label use. Educational content, not medical advice. Page medically reviewed by Teja V. Surapaneni, MD, MS (NV, WA, OR, WY). Last reviewed: April 17, 2026