Rapamycin
mTOR Inhibitor | Longevity & Immunosuppression
Rapamycin (sirolimus) is a macrolide compound originally discovered in 1972 from a soil bacterium (Streptomyces hygroscopicus) found on Easter Island (Rapa Nui). It was FDA-approved in 1999 as an immunosuppressant for the prevention of organ transplant rejection and has since become the most studied pharmacological intervention for lifespan extension. Rapamycin is the only drug that has consistently extended lifespan in every organism tested, including yeast, worms, flies, and mice, making it the benchmark compound in longevity research. At immunosuppressive doses (daily administration), it prevents transplant rejection and treats certain cancers. At lower pulsed doses (weekly administration), it is increasingly used off-label in the longevity community to target aging-related pathways while minimizing immunosuppressive side effects. The distinction between daily immunosuppressive dosing and weekly pulsed longevity dosing is critical, as the side effect profiles differ substantially between these two regimens.
Moleküler Gösterim
M.W.: 914.17 Da
PubChem 2D yapı diyagramı
Referans Flakon
Referans illüstrasyonu — ürün listesi değildir
Etki Mekanizması
Rapamycin exerts its effects by binding to the intracellular protein FKBP12, forming a complex that directly and specifically inhibits mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is a master nutrient-sensing kinase that integrates signals from growth factors, amino acids, energy status, and stress to regulate cell growth, proliferation, and metabolism. When mTORC1 is active, it promotes anabolic processes including protein synthesis (via S6K1 and 4E-BP1 phosphorylation), lipid synthesis, and nucleotide synthesis while suppressing autophagy. By inhibiting mTORC1, rapamycin shifts the cellular balance from growth toward maintenance and repair: it upregulates autophagy (cellular self-cleaning), enhances mitochondrial function, reduces senescent cell accumulation, improves proteostasis, and reduces chronic low-grade inflammation (inflammaging). With chronic daily dosing, rapamycin can also inhibit mTORC2, which mediates Akt signaling and is responsible for some of the metabolic side effects (insulin resistance, lipid changes). Pulsed weekly dosing preferentially inhibits mTORC1 while allowing mTORC2 to recover between doses, which is believed to account for the improved side effect profile of longevity protocols.
Rapamycin (sirolimus) is a macrolide compound originally discovered in 1972 from a soil bacterium (Streptomyces hygroscopicus) found on Easter Island (Rapa Nui). It was FDA-approved in 1999 as an immunosuppressant for the prevention of organ transplant rejection and has since become the most studied pharmacological intervention for lifespan extension. Rapamycin is the only drug that has consistently extended lifespan in every organism tested, including yeast, worms, flies, and mice, making it the benchmark compound in longevity research. At immunosuppressive doses (daily administration), it prevents transplant rejection and treats certain cancers. At lower pulsed doses (weekly administration), it is increasingly used off-label in the longevity community to target aging-related pathways while minimizing immunosuppressive side effects. The distinction between daily immunosuppressive dosing and weekly pulsed longevity dosing is critical, as the side effect profiles differ substantially between these two regimens.
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| Hedef | Doz | Sıklık | Yol |
|---|---|---|---|
| MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 10 HOURS 28 MINUTES 43 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE | 5-6 mg once weekly | MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 10 HOURS 58 MINUTES 19 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE | MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 11 HOURS 02 MINUTES 18 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE |
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| MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 10 HOURS 28 MINUTES 43 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE | 8-10 mg every two weeks | MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 10 HOURS 28 MINUTES 43 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE | MYMEMORY WARNING: YOU USED ALL AVAILABLE FREE TRANSLATIONS FOR TODAY. NEXT AVAILABLE IN 11 HOURS 02 MINUTES 18 SECONDS VISIT HTTPS://MYMEMORY.TRANSLATED.NET/DOC/USAGELIMITS.PHP TO TRANSLATE MORE |
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Kaynaklar
- Rapamycin fed late in life extends lifespan in genetically heterogeneous mice — Harrison, D.E., Strong, R., Sharp, Z.D., et al.
- mTOR inhibition improves immune function in the elderly — Mannick, J.B., Del Giudice, G., Lattanzi, M., et al.
- mTOR is a key modulator of ageing and age-related disease — Johnson, S.C., Rabinovitch, P.S., Kaeberlein, M.
- Rapamycin for longevity: opinion article — Blagosklonny, M.V.
- PEARL Trial: Participatory Evaluation of Aging with Rapamycin for Longevity — Kraig, E., Linehan, L.A., Liang, H., et al.