The rapamycin-mtor intervention entry has been updated to reflect RAPA-EX-01, the first published RCT pairing weekly sirolimus (6 mg) with a 13-week structured exercise program in older adults.

Changes to the public entry:

• shortDescription now leads with the RCT finding (no benefit on primary endpoint, no methylation-clock signal).
• keyFindings includes the per-protocol result: placebo + exercise outperformed rapamycin + exercise on the 30-second chair-stand test (p=0.007, Cohen's d=-0.90).
• clockResponsiveness updated: methylation clocks showed no significant difference between arms.
• whatWeDontKnow and practicalNotes rebalanced to reflect this human-trial null.

Tier (PROMISING) and category (therapeutic) unchanged.

RAPA-EX-01 (Stanfield, Kaeberlein, et al., J Cachexia Sarcopenia Muscle 2026) is the first published randomized, double-blind, placebo-controlled trial testing the hypothesis that weekly mTORC1 inhibition enhances functional and biological aging response to structured exercise in older adults.

The primary hypothesis failed: the placebo + exercise arm outperformed the rapamycin + exercise arm on lower-extremity function (p=0.007, large effect size favoring placebo). Secondary endpoints (grip, walk, CRP, methylation clocks) were all null.

This RCT is significant because the longevity community (including authors Stanfield and Kaeberlein, known rapamycin advocates) had pinned hopes on intermittent rapamycin as a synergistic complement to exercise. The negative finding warrants a rebalance of the public-facing copy — not a tier drop (animal evidence is unchanged), but a shift from forward-leaning anticipation ("early trials exploring") to evidence-led caution ("first published RCT found no benefit").

Readers considering intermittent rapamycin for aging will now see that the most popular protocol (weekly dosing + exercise) failed its primary outcome in a published RCT. They should understand:

1. This is one 3-month RCT in 40 older adults — replication is needed before firm conclusions.
2. Tier remains PROMISING due to robust animal lifespan evidence.
3. The rapamycin case for humans still rests on mechanism (mTOR inhibition) and animal lifespan data, not yet on human longevity or functional endpoints.
4. Other dosing schedules or populations are not directly tested by this trial.

This update raises the evidential bar and encourages cautious interpretation rather than adoption of an unproven protocol.