Rapamycin (sirolimus) is a macrolide discovered in Easter Island soil bacteria. Used clinically as an immunosuppressant; explored extensively off-label for longevity.
Mechanism — Inhibits mTORC1, the cellular growth and nutrient-sensing pathway. Induces autophagy, reduces senescent cell burden, and extends lifespan in yeast, worms, flies, and mammals. Effects are dose- and dosing-frequency dependent.
Use case — Off-label longevity (typical 5-8 mg once weekly). Lifestyle clinics increasingly prescribe; PEARL trial enrolled to evaluate. Patient cohort tracking by Dr. Alan Green and others suggests good tolerability.
Caveats — Immunosuppression at high or chronic dosing. Mouth ulcers, dyslipidemia, glucose elevation in some. Weekly pulsing minimizes immunosuppression while preserving autophagy. Don't use during active infection or vaccination periods. Long-term human longevity benefits are inferred, not yet proven.