Rapamycin
Rapamycin (Sirolimus)
Rapamycin (sirolimus) is an mTOR (mechanistic target of rapamycin) inhibitor originally developed as an immunosuppressant for organ transplant recipients, now extensively studied as a potential longevity and healthspan-extending compound. It is used clinically to prevent organ rejection and treat certain cancers, and is being explored off-label by longevity-focused physicians at low intermittent doses for its geroprotective effects observed consistently across multiple animal models.
Mechanism of Action
Rapamycin binds to the intracellular protein FKBP12, and this complex directly inhibits mTORC1 (mechanistic target of rapamycin complex 1), a central nutrient-sensing kinase that regulates cell growth, protein synthesis, and autophagy. By suppressing mTORC1 activity, rapamycin promotes autophagy (cellular cleanup of damaged proteins and organelles), reduces senescent cell burden, and mimics aspects of caloric restriction at the molecular level. Chronic or high-dose exposure can also partially inhibit mTORC2, which is associated with glucose metabolism disruption and immune compromise.
Evidence by Health Goal(18 goals)
Dosing Protocols
With a high-fat meal to improve bioavailability
Cycle: Continuous weekly dosing; some protocols use 3 weeks on, 1 week off
Intermittent weekly dosing (rather than daily) is the dominant longevity protocol, intended to allow mTORC2 recovery between doses. The 5mg/week dose is most commonly reported in longevity-focused physician communities. Daily dosing is reserved for transplant and oncology indications and carries substantially higher risk.
Safety & Side Effects
Rapamycin is a prescription-only medication in the US and most countries with a well-characterized but meaningful side effect profile; intermittent low-dose longevity protocols appear substantially safer than transplant-level daily dosing, but rigorous human longevity trial data are still limited. Use should be supervised by a physician with baseline and periodic monitoring of CBC, lipid panel, fasting glucose, and renal function, as immunosuppression and metabolic side effects remain real risks even at low doses.
Possible Side Effects
- !Mouth sores (oral ulcers/stomatitis) - most common at any dose
- !Impaired wound healing and increased infection susceptibility
- !Dyslipidemia - elevated triglycerides and LDL cholesterol
- !Glucose intolerance and insulin resistance with prolonged use
- !Mild fatigue and malaise, particularly in the days following each dose
- !Edema (peripheral fluid retention)
- !Thrombocytopenia (reduced platelet count) at higher doses
- !Interstitial pneumonitis (rare but serious, particularly at higher doses)
Interactions
- -Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit juice) dramatically increase rapamycin blood levels - potentially dangerous combination
- -Strong CYP3A4 inducers (rifampin, St. John's Wort, phenytoin) significantly reduce rapamycin levels, reducing efficacy
- -Concurrent immunosuppressants or corticosteroids compound immunosuppression and infection risk
- -Metformin co-administration is common in longevity stacks but may have additive mTOR-suppressing effects; monitor for excess metabolic impact
- -Live vaccines are contraindicated during use due to immunosuppression; attenuated vaccines may have reduced efficacy
Cost & Where to Buy
Cost varies widely based on whether obtained via prescription (brand Rapamune is expensive; generic sirolimus is more affordable) or compounding pharmacy. Generic sirolimus at 1mg tablets for weekly 5mg dosing runs approximately $40-80/month at compounding pharmacies; brand-name Rapamune can exceed $200/month even for low-dose protocols. Prescription required in the US.
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