Rankings / Longevity — Pharma (Off-Label)
Rapamycin (sirolimus)
Longevity · mTOR inhibitor
Tier C
Bottom line
Read Off Label grades Rapamycin (sirolimus) as C (5.0/10) based on moderate-weak evidence, med-high benefit magnitude, and a med-risk safety profile.
ITP: single most reproducible life-extending compound in mammals.
Typical use: 5-10 mg PO weekly (off-label longevity dosing); much higher for transplant — Rx.
What this is
ITP: single most reproducible life-extending compound in mammals. PEARL trial (Moel et al, Aging April 2025; n=114, 48 weeks, 5 or 10 mg weekly): MISSED primary endpoint of visceral adiposity reduction (η²=0.001, p=0.94) and most biomarkers unchanged. Secondary signals: lean tissue mass and self-reported pain improved in women on 10 mg; emotional well-being and general health improved at 5 mg. Adverse events similar to placebo — confirming safety at these doses. Most discussed longevity drug but human efficacy data remains underwhelming.
Mechanism
Binds FKBP12; inhibits mTORC1 — the central nutrient-sensing kinase complex; induces autophagy; reduces protein synthesis; intermittent dosing may spare mTORC2
Dose & route
5-10 mg PO weekly (off-label longevity dosing); much higher for transplant
Citations
- https://doi.org/10.18632/aging.206235
- https://www.nature.com/articles/nature08221
- https://www.aging-us.com/article/206300/text
- https://pubmed.ncbi.nlm.nih.gov/40554265/
- https://pubmed.ncbi.nlm.nih.gov/40426219/
- https://clinicaltrials.gov/study/NCT02332902
- https://pubmed.ncbi.nlm.nih.gov/41789635/
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Common questions
- Does Rapamycin (sirolimus) work?
- Read Off Label rates the evidence for Rapamycin (sirolimus) as Moderate-Weak and the benefit magnitude as med-high, producing an overall grade of C (5.0/10). ITP: single most reproducible life-extending compound in mammals.
- Is Rapamycin (sirolimus) safe?
- Rapamycin (sirolimus) has a med risk profile in published human data. Legal status: Rx (off-label for longevity). This is not medical advice — see the disclaimer.
- What is the typical dose for Rapamycin (sirolimus)?
- 5-10 mg PO weekly (off-label longevity dosing); much higher for transplant
- How does Rapamycin (sirolimus) work?
- Binds FKBP12; inhibits mTORC1 — the central nutrient-sensing kinase complex; induces autophagy; reduces protein synthesis; intermittent dosing may spare mTORC2
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.