Rankings / Longevity — Pharma (Off-Label)

Rapamycin (sirolimus)

Longevity · mTOR inhibitor

Tier C

Reviewed by Read Off Label · Last reviewed · How we grade

mtor-inhibitionautophagyprescription
5 / 10
Tier C
Ev 4.5 Bn 6.5 Sf 5

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.

Studied, labeled, or reported-use context: 5-10 mg PO weekly (off-label longevity dosing); much higher for transplant — Rx; not individualized guidance.

Frontier potential — editorial judgment, not evidence

This is a separate axis from the grade above. It asks a different question: if this worked in humans, how much would it matter? It is our judgment, it is not part of the composite score, and it cannot raise a grade. A high number here is a statement about the idea, not about whether it works or whether anyone should take it.

9/10
Field-defining if it translates Phase 2

What the ceiling rests on

The most reproducible lifespan extension in mammalian biology: the NIA Interventions Testing Program extended median lifespan in genetically heterogeneous mice across three independent sites, in both sexes, and even when started in late life. The mTOR pathway it targets is conserved and central to nutrient sensing.

Why it may not get there

No human trial has ever measured a lifespan or mortality endpoint, and PEARL — the first randomised healthspan trial — missed its primary endpoints. Chronic immunosuppression, impaired glucose tolerance, and impaired wound healing are documented in transplant use, and the intermittent low-dose schedules the longevity community uses have never been shown to preserve the benefit while avoiding those effects.

What would change this A randomised trial with a hard clinical endpoint rather than a biomarker panel.

If you were testing this on yourself

Two properties decide whether an n-of-1 experiment is readable and recoverable. These describe the experiment — they are not a judgment about whether to run it, and nothing here is a recommendation.

Can you undo it?

Slow to reverse

Immunosuppression and metabolic effects resolve after stopping, but the drug has a long half-life and impaired wound healing persists while levels fall. Not an acute on-off.

Can you tell if it worked?

Nothing you can measure

No endpoint exists that you could observe for the reason this is taken. An experiment without a readout cannot tell you anything, however it turns out.

What would fool you There is no endpoint for the longevity use that a person can observe on any human timescale — this is the clearest example on the site of a compound that cannot be self-tested for the reason it is taken. Biological-age clocks are sometimes used as a proxy; they are not validated as outcome surrogates, and treating a clock reading as evidence the drug worked is a measurement error rather than a result.

What the evidence says

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

Studied, labeled, or reported dose & route

5-10 mg PO weekly (off-label longevity dosing); much higher for transplant

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about Rapamycin (sirolimus)'s effects?
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.
What safety findings are reported for Rapamycin (sirolimus)?
Rapamycin (sirolimus) has a med risk profile in the database. Med (immunosuppression, mouth sores, hyperlipidemia, insulin resistance, wound healing impairment) Legal status: Rx (off-label for longevity).
What doses or routes are reported for Rapamycin (sirolimus)?
5-10 mg PO weekly (off-label longevity dosing); much higher for transplant This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
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.