INDICATIONS FOR USE

Rapamycin (Sirolimus) is used off-label in longevity and regenerative medicine for its potential anti-aging and healthspan-extending effects. It is commonly employed by physicians and researchers to help modulate cellular aging, improve metabolic and mitochondrial efficiency, and reduce chronic inflammation associated with aging (“inflammaging”). Additional proposed benefits include improved immune resilience, enhanced autophagy, and potential protection against age-related diseases such as cardiovascular disease, neurodegeneration, and cancer.

ROUTE OF ADMINISTRATION

• Oral capsule or tablet

COMMON INITIAL DOSING REGIMENS

• A common off-label regimen in longevity protocols is 5–10 mg taken orally once weekly, with or without food. Some practitioners use lower starting doses (1–3 mg weekly) and titrate gradually to assess tolerance. Intermittent dosing schedules are used to reduce side effects and to allow periodic recovery of normal mTOR signaling. Continuous daily dosing, as used in transplant or oncology settings, is not recommended for longevity applications.

MECHANISM OF ACTION

• Rapamycin selectively inhibits the mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of cellular growth, metabolism, and aging. By suppressing mTORC1, rapamycin promotes autophagy (the body’s natural cellular repair and cleanup process), reduces oxidative stress, and may preserve stem cell function. This modulation of nutrient-sensing pathways is believed to slow biological aging, improve metabolic flexibility, and enhance immune function. At higher or continuous doses, rapamycin also inhibits mTORC2, which can affect insulin sensitivity and lipid metabolism; thus, longevity dosing aims to intermittently and selectively inhibit mTORC1 only.

COMMON SIDE EFFECTS

• General: Mouth ulcers (aphthous stomatitis), mild fatigue, gastrointestinal upset, or headaches.

• Metabolic: Possible mild elevations in cholesterol or triglycerides.

• Immune: Increased susceptibility to infection if overdosed or used too frequently.

• Dermatologic: Occasional acne, rash, or delayed wound healing.

• Rare: Severe infections, anemia, or thrombocytopenia at immunosuppressive doses.

CONTRAINDICATIONS

• Absolute: Known hypersensitivity to rapamycin or its excipients.

• Relative: Active infection, poor wound healing, or concurrent use of strong CYP3A4 inhibitors or inducers. Use with caution in individuals with uncontrolled hyperlipidemia or diabetes, as rapamycin can transiently alter glucose and lipid metabolism.

COMPARISON WITH OTHER AGENTS

• Metformin: Both agents are studied for potential longevity benefits through nutrient-sensing and metabolic pathways. Rapamycin primarily targets mTOR, whereas metformin acts via AMPK activation and mitochondrial modulation.

• NAD+ precursors (NMN, NR): These enhance cellular energy production and DNA repair through sirtuin activation; rapamycin influences longevity through autophagy and protein turnover rather than energy cofactor replenishment.

• Senolytics (e.g., fisetin, dasatinib + quercetin): These remove senescent cells directly, whereas rapamycin suppresses the pro-inflammatory secretions (SASP) of senescent cells and delays their formation.

EXPERIMENTAL TREATMENT DISCLAIMER:

• Rapamycin is FDA-approved only for specific medical indications such as organ transplantation and certain cancers. Its use for longevity, metabolic optimization, or anti-aging purposes is off-label and experimental. While animal studies and early human research suggest potential benefits in extending healthspan and improving cellular function, the long-term safety, optimal dosing, and efficacy of rapamycin for aging-related indications have not been established. By electing to use rapamycin for these purposes, the patient acknowledges the experimental nature of the therapy and assumes all associated risks.

LEARN MORE

• Evidence hound? Review our comprehensive listing of PubMed direct links to original research related to this medication.