Rapamycin — mTOR (mechanistic target of rapamycin) inhibitor — macrolide antibiotic / FDA-approved immunosuppressant with longevity off-label use

Rapamycin (sirolimus) is a macrolide produced by Streptomyces hygroscopicus that binds FKBP12 to form a complex that allosterically inhibits mTORC1 (mechanistic Target Of Rapamycin Complex 1). mTORC1 is a master regulator of anabolic metabolism: it promotes protein synthesis, inhibits autophagy, and drives cellular growth. Chronic mTORC1 overactivation contributes to aging-associated pathologies (senescence, metabolic syndrome, cancer). Longevity rationale: (1) The NIA Interventions Testing Program showed 9–14% lifespan extension in mice even when started late in life (600 days); (2) Mannick et al. (2014, 2018 PLOS Biology/Science Translational Medicine) demonstrated that a 6-week course of everolimus (rapalog) improved vaccine response by 20% and reduced infections in elderly humans — direct anti-aging immune benefit; (3) mTORC1 inhibition activates autophagy (cellular self-cleaning), reduces senescent cell accumulation, and restores immune function. CRITICAL: Rapamycin also partially inhibits mTORC2 with chronic/continuous dosing — this is responsible for insulin resistance and metabolic side effects. Intermittent dosing (once weekly) spares mTORC2 and retains mTORC1 inhibition benefits.

نظرة عامة

هذه الصفحة جزء من مكتبة المركّبات المُصنَّفة بالأدلة في Hormonaly. جميع الادعاءات السريرية مرتبطة بمصادر علمية مُحكَّمة عبر خط أنابيب التحقق المزدوج للاستشهادات.

فئة المركّب

mTOR (mechanistic target of rapamycin) inhibitor — macrolide antibiotic / FDA-approved immunosuppressant with longevity off-label use

آلية العمل

Rapamycin (sirolimus) is a macrolide produced by Streptomyces hygroscopicus that binds FKBP12 to form a complex that allosterically inhibits mTORC1 (mechanistic Target Of Rapamycin Complex 1). mTORC1 is a master regulator of anabolic metabolism: it promotes protein synthesis, inhibits autophagy, and drives cellular growth. Chronic mTORC1 overactivation contributes to aging-associated pathologies (senescence, metabolic syndrome, cancer). Longevity rationale: (1) The NIA Interventions Testing Program showed 9–14% lifespan extension in mice even when started late in life (600 days); (2) Mannick et al. (2014, 2018 PLOS Biology/Science Translational Medicine) demonstrated that a 6-week course of everolimus (rapalog) improved vaccine response by 20% and reduced infections in elderly humans — direct anti-aging immune benefit; (3) mTORC1 inhibition activates autophagy (cellular self-cleaning), reduces senescent cell accumulation, and restores immune function. CRITICAL: Rapamycin also partially inhibits mTORC2 with chronic/continuous dosing — this is responsible for insulin resistance and metabolic side effects. Intermittent dosing (once weekly) spares mTORC2 and retains mTORC1 inhibition benefits.

الوضع التنظيمي

FDA APPROVED for: kidney/liver/heart transplant rejection, lymphangioleiomyomatosis (LAM), TSC-associated tumors. All longevity use is OFF-LABEL. Not scheduled as controlled substance in US.

مستوى الأدلة

B — FDA-approved for transplant/LAM/TSC with strong Phase 3 data. For longevity: Mannick 2014 Phase 2a (n=218, everolimus improved vaccine response p<0.001); Mannick 2018 (n=264, everolimus reduced infections in elderly). PEARL trial (intermittent rapamycin in aging adults, n=159) ongoing as of 2024 (NCT04488601). No completed Phase 3 longevity RCT yet.