RAPA-EX-01: First RCT of weekly sirolimus + exercise in older adults

Correction recorded 12 October 2026. This May update previously emphasized the per-protocol p=.007 result. The primary intention-to-treat analysis was nonsignificant (p=.089; difference −2.13 chair stands, 95% CI −4.61 to 0.34). Per-protocol results are now identified as sensitivity analyses. The effective date has been corrected to the paper's first publication date, 15 April 2026. The original May publication timestamps are preserved.

RAPA-EX-01 randomized 40 older adults during 13 weeks of matched home exercise. It did not demonstrate added functional benefit from sirolimus; sensitivity analyses suggested smaller gains. Four methylation measures showed no statistically significant between-group differences. Adverse-event counts were 99 versus 63, with a nonsignificant rate comparison and one possibly related hospitalized pneumonia. The authors' advocacy cannot establish freedom from bias; disclosed interests and study methods matter.

Read the primary analysis before the sensitivity results. Neither nonsignificant clock comparisons nor a small short-term safety sample establishes equivalent effects or long-term safety. The intervention's current Emerging rating concerns human aging benefit; animal lifespan evidence is a separate endpoint. This correction does not recommend a treatment or dosing protocol.