Rapamycin
Sirolimus
Overview
Rapamycin (Sirolimus) is a macrolide compound originally discovered in soil bacteria from Easter Island (Rapa Nui) that functions as a potent mTOR inhibitor. It is FDA-approved as an immunosuppressant for organ transplantation and has been investigated extensively in longevity research after demonstrating lifespan extension in multiple model organisms including mice — the most robust pharmacological longevity intervention identified to date. It is currently in human clinical trials for aging-related conditions through the Interventions Testing Program and multiple academic centers. Rapamycin sits at the center of modern longevity science.
Compound Data
Molecular Formula
C51H79NO13
Molecular Weight
914.20 g/mol
IUPAC Name
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
PubChem CID
5284616Where does Rapamycin sit?
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Mechanism of Action
Rapamycin works by forming a complex with the intracellular protein FKBP12, which then binds to and inhibits mTORC1 — the mechanistic target of rapamycin complex 1. mTORC1 is a master regulator of cell growth, protein synthesis, and autophagy. By inhibiting mTORC1, rapamycin shifts cellular metabolism from growth mode to maintenance and repair mode, enhancing autophagy (cellular self-cleaning), reducing senescent cell accumulation, and improving stress resistance. These effects closely mimic the longevity-promoting effects of caloric restriction at the molecular level. In animal models, rapamycin extended median lifespan by 9-14% even when started late in life. Partial mTOR inhibition through intermittent dosing is being investigated to capture longevity benefits while minimizing immunosuppressive side effects.
Dosage Information
Typical Dose
1-6 mg weekly (longevity protocols)
Frequency
Once weekly (longevity use) or daily (transplant immunosuppression)
Administration
Oral tablet
Notes
Longevity dosing protocols are not FDA-approved. Weekly intermittent dosing is used in research contexts to minimize side effects. Requires medical supervision and monitoring of lipid levels and immune function.
Potential Side Effects
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Quick Facts
- Administration
- Oral tablet
- Typical Dose
- 1-6 mg weekly (longevity protocols)
- Frequency
- Once weekly (longevity use) or daily (transplant immunosuppression)
- References
- 0 curated + 49 from PubMed
- Clinical Trials
- 49 registered
- Evidence Score
- 71.4 / 100