Human lifespan evidence: none
Cross-reference: Sirolimus and rapamycin are the SAME molecular compound: 'rapamycin' is the research-literature name and 'sirolimus' is the INN/generic drug name used on FDA labeling. This page exists as a separate URL for the drug-name search context (per the sourcing brief's page list) and duplicates the /rapamycin evidence entries rather than presenting independent evidence. See /rapamycin for the full evidence map, including the RTB101 rapalog-class context.
Classification
Intervention class: mTOR inhibitor (macrolide; direct FKBP12-mediated mTORC1 inhibitor) -- FDA generic/INN drug name for the same molecular entity as rapamycin
Aliases: Rapamycin (research-literature name for the same molecule), Rapamune (brand)
Relationship to mTOR: Direct allosteric inhibitor of mTORC1 via the FKBP12-rapamycin(sirolimus) complex. Acute exposure is highly mTORC1-selective; chronic/high-dose exposure can also disrupt mTORC2 assembly.
Mechanism summary: Binds FKBP12; the FKBP12-sirolimus complex binds the FRB domain of mTOR within mTORC1, allosterically inhibiting mTORC1 kinase output toward S6K1 (Thr389) and 4E-BP1, and reducing ULK1/TFEB-mediated autophagy suppression. See /mtorc1-vs-mtorc2 for the full complex-level input/output map.
Regulatory status
FDA-approved prescription immunosuppressant (renal transplant rejection prophylaxis, brand Rapamune; sirolimus is also used in coated coronary stents and lymphangioleiomyomatosis). NOT approved for any anti-aging, longevity, or healthspan indication in any jurisdiction as of this dataset's literature-search date. No 'longevity dose' or cycling protocol is an FDA-recognized or clinically established regimen.
Evidence per species / population (5-qualifier claim format)
Mouse (Mus musculus, UM-HET3, NIA Interventions Testing Program) — Same compound and same ITP study as documented on /rapamycin; duplicated here for the sirolimus generic-drug-name search context, not independent evidence. Tier 5 · Replicated animal lifespan verification: verified_2026-07-11
1. Species / populationGenetically heterogeneous UM-HET3 mice, multiple test sites (NIA ITP)
2. Exposure, route, schedule~14 ppm in chow, initiated at ~600 days of age (late-life start)
3. Comparator & durationControl chow, same-age cohort; followed to natural death
4. Endpoint & numeric resultAge at 90% mortality (90th-percentile lifespan) increased +14% (female) / +9% (male) at ~14 ppm in chow, initiated at ~600 days of age. Replicated across 3 independent ITP test sites. Median lifespan was also increased. The 42-ppm dose-response result is a separate 2014 study and is shown as its own row below.
5. What this study did NOT establishDid not test human lifespan, human dosing equivalence, or safety of any 'anti-aging' dose in humans. Same underlying compound and study as the /rapamycin page; not independent confirmation.
Mouse (Mus musculus, UM-HET3, NIA ITP dose-response, Miller 2014) — Miller et al., Aging Cell 2014 (PMID 24341993). Kept as its own evidence row because it is a different study, a different dose and a different endpoint metric from the 2009 report. Tier 5 · Replicated animal lifespan verification: verified_2026-07-11
1. Species / populationGenetically heterogeneous UM-HET3 mice, NIA ITP dose-response study
2. Exposure, route, schedule42 ppm rapamycin in chow -- threefold the ~14 ppm dose used in the 2009 report
3. Comparator & durationControl chow, same-age cohort; followed to natural death
4. Endpoint & numeric resultMEDIAN lifespan +26% (female) / +23% (male) at 42 ppm; maximal lifespan also increased in both sexes. Rapamycin increased lifespan more in females than in males at every dose tested.
5. What this study did NOT establishDid not test human lifespan, human dose equivalence, or the safety of any 'anti-aging' dose in humans. A threefold dose increase in mice does not establish a human dose-response relationship. This is a separate study from the 2009 report above and measures median lifespan, not 90%-mortality age -- the two results must not be pooled. Same compound and same studies as /rapamycin; not independent confirmation.
Negative / null / conflicting findings
PEARL trial: 48-week rapamycin (sirolimus-class compound) RCT, primary endpoint (visceral fat) showed no significant effect (eta-squared = 0.001, p = .942). [study record] verification: verified_2026-07-11
Safety
Safety notes
Sirolimus is a prescription immunosuppressant. Approved-use labeling carries warnings for increased infection risk, malignancy/lymphoma risk, stomatitis, and (with related rapalogs) non-infectious pneumonitis. These warnings apply to approved immunosuppressive use; safety of any off-label 'longevity' dosing schedule has not been established and is not published on this site.
Source: Sirolimus/Rapamune prescribing information (FDA/DailyMed) (regulatory label) verification: verified_2026-07-11
Editorial policy: This site publishes no 'longevity dose', no cycling protocol, no dosing calculator, and no acquisition guidance for sirolimus, per Nabus Research YMYL editorial policy.
Funding / conflict of interest
Funding sources and conflict-of-interest disclosures for individual studies are not reproduced here pending primary-source verification; see each linked study record.
Related study records
Version 0.2.0-mvp · literature search date 2026-07-11 · editorial owner Nabus Research