Rapamycin (Sirolimus)

The undisputed champion of mammalian life extension in the lab.

Originally discovered in the soil of Easter Island (Rapa Nui), Rapamycin is an FDA-approved immunosuppressant used for organ transplants. In longevity medicine, it is prescribed off-label in pulsed doses to inhibit mTOR (mechanistic Target of Rapamycin).

Mechanism of Action

mTOR is a nutrient-sensing pathway. When nutrients are abundant, mTOR is active, promoting cellular growth. When inhibited (by fasting or Rapamycin), the cell enters a conservation state, activating autophagy—the process of clearing out damaged cellular components (like misfolded proteins and senescent cells).

The Evidence Base

The Interventions Testing Program (ITP) showed that Rapamycin extended median lifespan in mice by up to 23% in males and 26% in females. It is the most robust, reproducible pharmacological intervention for lifespan extension to date.

Dosing Protocols

Daily dosing causes immune suppression. For longevity, doctors prescribe pulsed, intermittent dosing to achieve peak blood levels (inhibiting mTORC1) while allowing a trough to avoid inhibiting mTORC2 (which causes side effects like insulin resistance).

• Common Protocol: 5mg to 6mg taken once weekly.
• Joan Mannick Trial Variant: Used RAD001 (an analog), equivalent to ~5mg weekly.

See our calculators to view standard weight-adjusted models.

Side Effects & Risks

Off-label use requires medical supervision. Common side effects include aphthous ulcers (canker sores), slight increases in lipid levels, and potential immune modulation.