Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results
What this study shows
The authors describe PEARL as the longest trial of rapamycin for healthy ageing so far: 48 weeks, once a week, ages 50 to 85, 114 people finished (40 on 5 mg, 35 on 10 mg, 39 on placebo). The question the trial was built to answer was visceral fat on a DXA scan, and that did not change. Most of what gets quoted comes from secondary results. Lean mass rose in women on 10 mg, and these women also reported less pain, but pain came from a questionnaire the authors did not list as an endpoint, and only eight women were in the 10 mg group, hence the very wide interval (odds ratio 28, 95% CI 2.4 to 324). Side effects were similar to placebo, with more stomach complaints on rapamycin. Bone density was the one signal pointing the wrong way: in the 5 mg group the odds of an improvement in bone mineral density were lower than on placebo (odds ratio 0.24, 95% CI 0.06 to 0.93, p = 0.04), but 10 mg showed no change (odds ratio 1.00) and the comparisons between groups were not significant. Boundary: the capsules were compounded, and the authors found they reached about a third of the blood level of the commercial drug, so 10 mg here is closer to 3 mg of generic sirolimus. Dosing was self-reported, and the group was about two thirds men and health-conscious.
At a glance
| Evidence type | H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H. |
| Study type | 2 - Human Clinical Trial |
| Model system | Humans, RCT, ages 50-85 (n=114 completed) |
| Journal | Aging (Albany NY) |
| Year | 2025 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.18632/aging.206235 · PMID 40188830 · Free full text (PMC12074816) |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Intermittent low-dose rapamycin (5/10 mg weekly, 48 wk) |
| Target | mTOR |
| Model | Human – RCT (PEARL, ages 50-85, n=114 completed) |
| Effect | Intermittent low-dose rapamycin was safe over 1 year; some healthspan gains (e.g. lean tissue in women at 10 mg) |
| Dose | Rapamycin (compounded), 5 mg/week or 10 mg/week orally, 48 weeks; randomized double-blind placebo-controlled. Note: compounded effective dose ~66% lower than the advertised dose. |
| Sample size | 114 completed: 40 at 5 mg/wk, 35 at 10 mg/wk, 39 placebo. Low female enrollment (35.1%). |
| Effect size | Primary endpoint (visceral adipose tissue) NOT met. Secondary: decreased bone mineral density (OR 0.24, 95% CI 0.06-0.93, p=0.04); increased lean tissue (esp. women at 10 mg); small HbA1c rise in 5 mg males (p=0.010). Overall safe/well tolerated over 1 year. |
| Limitations | Small n -> wide 95% CIs / underpowered; low female enrollment; compounded-dose uncertainty; minor changes in RBC / BUN / HbA1c; human gerotherapeutic data still limited. |
In the Atlas
Related topics
Open questions that cite this study
- Cited as supporting evidence for the open question Does mTORC1-selective dosing extend lifespan, and is rapamycin's glucose intolerance a cost at all?.
- Cited as supporting evidence for the open question Muscle-sparing, pulsed mTORC1 inhibition.
- Cited as supporting evidence for the open question A sensor/autophagy biomarker panel as a surrogate endpoint for human trials.
- Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): a male-mouse survival signal from cross-cohort comparison, untested in humans.
Answers that reference this study
- Discussed in the plain-language answer How is rapamycin dosed in the longevity studies?.
- Discussed in the plain-language answer Does rapamycin extend lifespan in humans?.
- Discussed in the plain-language answer What are rapamycin's side effects?.
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Learn the biology
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