Rapamycin
| Category | Compounds |
|---|---|
| Also known as | Sirolimus, AY-22989 |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | longevitymtor-inhibitorimmunosuppressantresearch |
Overview
Rapamycin, known medically as sirolimus, is a macrolide compound originally isolated from a soil bacterium on Easter Island (Rapa Nui). It is FDA-approved as an immunosuppressant following kidney transplantation and has additional approved and investigational uses in lymphangioleiomyomatosis, drug-eluting stents, and various cancers. In longevity research, it is one of the most robustly characterized interventions shown to extend lifespan across multiple model organisms.
Rapamycin's pharmacology centers on inhibition of mTOR (mechanistic target of rapamycin), a master regulator of cell growth, protein synthesis, and autophagy. In aging research, acute low-dose and intermittent regimens are distinguished from the chronic immunosuppressive dosing used in transplant medicine, because the two paradigms produce different effects on complex 1 (mTORC1) versus complex 2 (mTORC2) signaling.
Rapamycin is widely discussed in longevity communities alongside peptides and compounds such as Klotho, FGF21, MOTS-c, Epitalon, NAD precursors, and TA-65. Although not a peptide, it is routinely cross-listed in research catalogs focused on aging biology.
Structure / Chemistry
Rapamycin is a macrocyclic lactone (molecular formula C51H79NO13, MW ~914 g/mol). It binds FKBP12 to form a complex that engages mTOR. Oral bioavailability is modest and variable, which has motivated development of analogs (rapalogs) including everolimus and temsirolimus.
Mechanism of Action
The rapamycin-FKBP12 complex allosterically inhibits mTORC1, reducing phosphorylation of downstream effectors S6K1 and 4E-BP1. The net effect is decreased protein synthesis, reduced cell growth, and increased autophagy. Prolonged or high-dose exposure also affects mTORC2, which influences AKT signaling and metabolic regulation.
Research Summary
| Area | Finding | Reference |
|---|---|---|
| Lifespan (mice) | Extended median and maximum lifespan | Harrison et al., Nature 2009 |
| Healthspan | Age-related pathology reductions | Wilkinson et al., Aging Cell 2012 |
| Immune | Improved flu vaccine response in elderly | Mannick et al., Sci Transl Med 2014 |
| Cardiac | Reversal of age-related cardiac dysfunction | Flynn et al., Aging Cell 2013 |
| Marmosets | Lifespan study in nonhuman primates | Ross et al., Aging Cell 2015 |
Pharmacokinetics
Rapamycin has a long elimination half-life (approximately 60-80 hours in humans), which makes intermittent dosing regimens attractive for longevity research. Oral bioavailability is variable, typically in the 10-20% range for the conventional formulation. Clinical immunosuppressive dosing differs substantially from the intermittent low-dose regimens studied in aging research. Dosing details are trial parameters, not guidance.
Common Discussion Topics
- mTORC1 vs. mTORC2 selectivity with different dosing schedules.
- Chronic immunosuppressive risks vs. intermittent longevity dosing.
- Comparison with dietary restriction and other longevity interventions.
- Potential for rapalogs with improved selectivity.
- Ongoing PEARL trial and related longevity research.
Related Compounds
Sourcing research-grade compounds
Obtaining high-purity, research-grade Rapamycin requires verified and trusted suppliers with third-party COA testing and transparent sourcing practices.
White Market Peptides — Verified Supplier →Join the discussion
See how the community is discussing Rapamycin. Share your experience, ask questions, and explore protocols on PepAtlas.
Related entries
- Epithalon— A synthetic tetrapeptide studied for telomerase activation, pineal gland regulation, and lifespan extension in animal models, based on decades of research by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology.
- FGF21— FGF21 is a liver-derived metabolic hormone of the fibroblast growth factor family that regulates energy balance, glucose handling, and macronutrient preference.
- Klotho— Klotho is an anti-aging protein that functions both as a membrane co-receptor and as a circulating hormone, with roles in phosphate handling, cognition, and longevity.
- MOTS-c— A 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene of mitochondrial DNA, identified as an exercise mimetic that activates AMPK signaling and regulates metabolic homeostasis.
- TA-65— TA-65 is a proprietary astragalus-derived compound, predominantly cycloastragenol, studied as a telomerase activator in aging research.