Longevity Next

Intervention

Sirolimus

Source-reviewed Last reviewed: 2026-10-02

Research Observatory

Evidence Update

Current evidence

Sirolimus trial findings remain regimen-specific: PEARL's primary visceral-fat comparison was null. RAPA-EX's primary intention-to-treat chair-stand comparison did not reach significance; prespecified sensitivity analyses favored placebo and some reached significance.

What changed

Adds regimen-specific trial findings and preserves the RAPA-EX sensitivity/safety cautions.

What did not change

These small trials do not establish a general longevity benefit, universal safety conclusion or definitive functional harm.

Why it matters

Different formulations, schedules and populations cannot be pooled into a universal recommendation.

Main limitation

Small studies, formulation/exposure differences, completer analysis and missing outcomes constrain generalization.

Next proof

Larger controlled studies with clear clinical endpoints and denominator audits.

Evidence reviewed through

Evidence release LNPG-REL-20261002-002

Sources

  1. NCT04488601 official trial record

    Source type registry Publication date 2020-07-28

    What this source establishes Identifies PEARL's registered arms, outcomes, status and actual enrollment of 129.

    Important limitation Registry enrollment is not the 114-person completer analysis; registration does not establish efficacy.

    Evidence access Official registry record reviewed.

  2. Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial.

    Source type primary_research_publication Publication date 2026-04-15

    What this source establishes Reports RAPA-EX-01's primary chair-stand comparison, sensitivity analyses and safety observations for sirolimus alongside exercise.

    Important limitation The primary intention-to-treat result was not significant; sensitivity findings cannot replace it or establish causal functional decline.

    Evidence access Relevant full-text sections reviewed.

  3. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.

    Source type primary_research_publication Publication date 2025-04-04

    What this source establishes Reports PEARL's null primary visceral-fat comparison and exploratory secondary and safety findings for weekly compounded rapamycin.

    Important limitation Completer analysis in a selected cohort; the full enrollment flow is unresolved and exposure cannot be equated with commercial formulations.

    Evidence access Relevant full-text sections reviewed.

Summary

Sirolimus trial findings remain regimen-specific: PEARL's primary visceral-fat comparison was null. RAPA-EX's primary ITT chair-stand comparison did not reach significance; prespecified sensitivity analyses favored placebo and some reached significance.

Intelligence Take

Different formulations, schedules and populations cannot be pooled into a universal recommendation.

Limitations

Small studies, formulation/exposure differences, completer analysis and missing outcomes constrain generalization.

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