Rapamycin
Also known as: Sirolimus · Rapamune · mTOR Inhibitor
The only compound proven to extend lifespan in every organism tested, from yeast to mammals, through inhibition of the mTOR pathway — the master regulator of cellular aging.
Overview
Rapamycin (sirolimus) is a macrolide compound originally discovered in soil bacteria on Easter Island (Rapa Nui). It is the most validated longevity compound in existence — the only drug that has consistently extended maximum lifespan in every organism tested, including yeast, worms, flies, and mice (by 9-26% in mice, even when started late in life). Its target, mTOR (mechanistic Target of Rapamycin), is now recognized as the central regulator of cellular aging. Rapamycin works by forming a complex with FKBP12 that inhibits mTORC1, a kinase complex that drives cell growth, protein synthesis, and suppresses autophagy. By inhibiting mTORC1, rapamycin enhances autophagy (cellular cleanup), reduces senescent cell accumulation, improves immune function (paradoxically, despite being an immunosuppressant at high doses), and reduces age-related inflammation.
The longevity community typically uses intermittent low-dose protocols (weekly dosing) to selectively inhibit mTORC1 while minimizing mTORC2 inhibition, which is associated with metabolic side effects. This approach has shown immune-enhancing effects in elderly humans, improving vaccine responses by 20%.
Mechanism of Action
Binds FKBP12 protein; the rapamycin-FKBP12 complex allosterically inhibits mTORC1 (but not acutely mTORC2). mTORC1 inhibition reduces S6K1 phosphorylation (decreasing protein synthesis), activates ULK1 (inducing autophagy), enhances TFEB nuclear translocation (lysosomal biogenesis), and derepresses 4E-BP1 (shifting translation toward stress-response genes). Chronic/high-dose use can also inhibit mTORC2, affecting Akt signaling and glucose metabolism.
Key Benefits
Potential Side Effects
Common Stacks
This peptide is commonly combined with the following compounds for synergistic effects:
Known Interactions
The following interactions have been documented for Rapamycin. Always consult a healthcare professional before combining compounds.
Use Caution (1)
Rapamycin (mTOR inhibitor) may blunt some of testosterone's anabolic/muscle-building effects since mTOR is required for muscle protein synthesis.
Synergistic (3)
Both are cornerstone longevity compounds. Metformin activates AMPK while rapamycin inhibits mTOR. Together they shift the body toward cellular repair and autophagy.
Rapamycin (mTOR inhibition) + Resveratrol (sirtuin activation) targets two key longevity pathways. Both promote autophagy and cellular maintenance.
FOXO4-DRI is a senolytic (clears senescent cells) while rapamycin inhibits mTOR to slow cellular aging. Complementary: clear damaged cells + slow aging of remaining cells.
Scientific References
Quick Reference
Typical Dose
3-6 mg once weekly (longevity protocol); varies widely
Frequency
Once weekly (most common longevity protocol)
Route
Oral tablet
Half-Life
~62 hours
Cycle Length
Ongoing or cyclical (e.g., 8 weeks on, 2 weeks off); highly individualized
FDA Status
FDA approved (Rapamune) for organ transplant rejection; off-label for longevity
Need to calculate dosing?
Use our reconstitution calculator to determine exact syringe measurements.
Open CalculatorThis information is for educational purposes only. Consult a qualified healthcare professional before using any peptide. Dosing information reflects commonly reported protocols and may not be appropriate for everyone.
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Metformin
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NAD+ precursors that restore declining cellular energy levels, activate sirtuins and PARPs, and support DNA repair — central to the biology of aging.
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A polyphenol compound found in red wine and grapes that activates SIRT1, enhances mitochondrial function, and provides cardiovascular and neuroprotective benefits.
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