Does rapamycin slow aging in humans? What the registered trials actually show

The registry, counted

ClinicalTrials.gov, searched on 2026-10-25 for rapamycin, sirolimus or everolimus against aging, returns 23 interventional records. Nineteen of them test an mTOR inhibitor as the intervention; the other four mention rapamycin only in a title or as a mechanistic tool (a metformin telomere study, a gene-therapy trial for muscle loss, a 2009 muscle-physiology study and a breast-cancer prevention trial). Across the 19, planned enrollment adds up to roughly 1,250 people. Twelve are recruiting, active or not yet open, one was withdrawn before it enrolled anyone, and six are complete.

Of the six completed trials, two are small topical-skin studies (10 and 22 people), one is a 13-person Mayo Clinic pilot in cardiac-rehab patients, one is the Wisconsin EVERLAST everolimus trial (106 people, completed July 2026, results not yet published), and two are randomised, placebo-controlled trials in healthy adults with results in print. Those two carry the entire human case for rapamycin as a longevity drug.

What is absent matters as much. No registered trial measures mortality, disease incidence or any hard outcome. The primary endpoints are visceral fat, T-cell counts, insulin sensitivity, drug levels in blood, ovarian reserve and bone density, which is the right design for this stage. It also means that anyone telling you rapamycin “extends human healthspan” is quoting mice: in the NIA Interventions Testing Program, rapamycin started at 600 days of age extended the lifespan of genetically mixed mice by 9% in males and 14% in females (Harrison et al., Nature 2009). That result is real and replicated. It is also a mouse result.

Trial one: 25 people, eight weeks, no signal

The first placebo-controlled trial in healthy older adults came from UT Health San Antonio (Kraig et al., Experimental Gerontology 2018; NCT02874924). Adults aged 70 to 95 took 1 mg of rapamycin or placebo daily for eight weeks; 25 were analysed, 11 on drug and 14 on placebo. The primary endpoint was T-cell function. There were no significant between-group differences in T-cell subsets, the PD-1 marker the mouse work predicted would fall did not fall, and cognition (three bedside tests), walking speed and grip strength did not change.

The safety ledger was reassuring but not blank. On rapamycin, haemoglobin, haematocrit and red-cell indices dropped (within reference ranges), HbA1c rose slightly (p = 0.032), and participants lost about 1.1 kg. Two people had diarrhoea, one a facial rash, one mouth sores. The authors concluded that short-term treatment appears safe in otherwise healthy older adults and that a larger, longer trial was needed. The work was NIH-funded; Pfizer supplied the drug.

The same group published a follow-on in Geroscience in September 2025: six men aged 70 to 76, open-label, 1 mg daily for eight weeks, with improved cardiac filling on MRI and better endothelial function. Six men and no placebo is a reason to run the next trial, not a reason to fill a prescription.

Trial two: PEARL, the crowdfunded trial behind the headlines

PEARL (Moel et al., Aging, April 2025; NCT04488601) is the largest completed rapamycin trial in healthy adults, and the one most often cited to sell it. Adults aged 50 to 85 took compounded rapamycin at 5 mg or 10 mg once a week, or placebo, for 48 weeks; 114 completed (40, 35 and 39 per arm). The sponsor was AgelessRx, a telehealth company that prescribes rapamycin; the money came mainly from crowdfunding through Lifespan.io; seven of the authors are AgelessRx employees and shareholders. The paper discloses all of this. Most of the coverage does not.

The registered primary endpoint was visceral fat on DXA. It did not change (p = 0.942). The findings in the headlines are secondary and sex-stratified: women on 10 mg gained lean mass versus placebo (mean difference 6.19, p = 0.018) and reported less pain, and the 5 mg group had lower odds of losing bone density (odds ratio 0.24, with a confidence interval that nearly touches 1). The authors state the trial was not powered for sex-stratified analysis and that replication is needed. The journal’s own press line was that low-dose rapamycin improves muscle mass and well-being. The trial’s own primary endpoint moved by nothing.

Safety: between 78% and 87% of participants in every arm, placebo included, reported an adverse event, and totals were similar across groups. Gastrointestinal symptoms were more frequent on drug (8 and 7 cases versus 4), and one person on 5 mg developed anaemia that needed a transfusion. Serious events were 1, 2 and 3 per arm. Over 48 weeks, in people screened to be healthy, nothing alarming surfaced; nothing was proven either.

The detail buyers should not skip: the compounded rapamycin used reached roughly one third of the blood concentration of the commercial tablet at 24 hours, and the authors put the equivalent effective dose of compounded forms about 66% lower. Much of the rapamycin sold through telehealth prescribers is compounded. A prescription that says 5 mg is not 5 mg of the drug the mouse and transplant studies used, unless someone has measured your blood level.

The bigger programme that already failed

The best-funded human test of low-dose mTOR inhibition for aging did not come from the longevity scene. It came from Novartis and its spin-out resTORbio. In 2014, Joan Mannick’s team reported that everolimus, a rapamycin analogue, improved the flu-vaccine response of adults over 65 by about 20% at a well-tolerated low dose (Science Translational Medicine; Novartis-funded). In 2018, a 264-person trial found that a low-dose combination of everolimus and the inhibitor RTB101 cut self-reported infections over the following year; everolimus alone showed only a non-significant trend.

The Phase 3 that followed, PROTECTOR 1 (NCT04668352), enrolled 1,024 adults aged 65 and over on RTB101 10 mg daily for 16 weeks through a winter. On 15 November 2019 resTORbio announced it had missed its primary endpoint, and the respiratory programme was halted. RTB101 is a cousin of rapamycin rather than rapamycin itself, so the failure does not close the question. It does show what happens when the hypothesis meets a properly powered trial: the signal that looked solid in 264 people did not survive in 1,024.

What the next three years will answer

Three NIA-backed trials are the ones to watch, and none has reported. EVERLAST (NCT05835999, University of Wisconsin) gave 106 insulin-resistant adults aged 55 to 80 everolimus at 0.5 mg daily or 5 mg weekly, or placebo, for 24 weeks, with insulin sensitivity as the primary endpoint; it completed in July 2026 and results are pending. RESTOR (NCT06658093, UT Health San Antonio) is enrolling 194 adults aged 65 to 90 to find the dose that restores youthful mTOR activity, then test six months of daily versus weekly dosing against placebo, with primary completion in July 2028. A second Wisconsin trial (NCT05949658, 72 people, to March 2027) compares sirolimus and everolimus for safety. A UT Southwestern dose study (60 adults, 2027) and Columbia’s 50-woman ovarian-aging trial (completed October 2025, unpublished) round out the near-term list.

Note what they are testing: dose, schedule and biomarkers. Daily low dose versus weekly higher dose is exactly the question the online rapamycin community currently answers by anecdote. The trials that will answer it with data are running now.

What it means if someone is selling it to you

Agewell does not score, rank or link rapamycin or any prescriber. It is a medical decision, not a checkout one. Rapamune (sirolimus) is FDA-approved to prevent kidney-transplant rejection and to treat lymphangioleiomyomatosis; at those doses its label carries a boxed warning on immunosuppression, infection and malignancy risk. Longevity use is off-label, at doses and schedules the label never studied, which is precisely why the trials above exist.

The trials’ own exclusion lists are a usable who-should-skip. PEARL and RESTOR excluded people with diabetes or poorly controlled glucose, impaired wound healing or surgery planned within a year, any immune deficiency or immunosuppressant use, chronic infections, uncontrolled lipids, kidney function below a GFR of 30, active cancer, and anyone taking drugs that interact with CYP3A4; PEARL also excluded premenopausal women. If you would have been screened out of the trial, you have no evidence base at all.

If you and a prescriber still decide to try, borrow the trial protocol rather than the forum protocol: baseline and repeat blood counts, lipids, glucose, HbA1c, liver and kidney panels; a named product (generic tablet or compounded, with a blood-level check if compounded); a written exit criterion before the first dose; and a stop date. Mouth sores and gut upset are the expected costs. And measure the boring ledger first: blood pressure, ApoB, HbA1c, body composition and a strength benchmark, as set out in our Baseline Month guide, carry more human evidence than any dose of rapamycin does today. Our purchases-to-skip guide covers the rest of the injectable and infusion menu.

The most honest way to take rapamycin in 2026 is inside a trial. RESTOR in San Antonio, the UT Southwestern study in Dallas and a University of Missouri trial for middle-aged ApoE4 carriers are recruiting. You get monitored dosing, measured blood levels and free labs, and the result counts for everyone who comes after you.

What we read

• ClinicalTrials.govRegistry search: rapamycin, sirolimus or everolimus for aging, interventional studies (23 records, checked 2026-10-25) →
• Aging (Albany NY) · Moel et al. (2025)PEARL results: no change in visceral fat; sex-stratified secondary findings; compounded rapamycin at about one third the blood concentration; AgelessRx conflicts →
• ClinicalTrials.gov · NCT04488601PEARL registration: primary endpoint visceral fat by DXA, adults 50-85, AgelessRx sponsor →
• Experimental Gerontology · Kraig et al. (2018)1 mg daily for 8 weeks in adults 70-95: no immune, cognitive or physical signal; haematology and HbA1c changes →
• Geroscience · Kellogg, Kraig et al. (2025)Open-label pilot in six men aged 70-76: cardiac and endothelial function after 8 weeks of 1 mg daily →
• Science Translational Medicine · Mannick et al. (2014)Everolimus improved influenza vaccine response in older adults by about 20%; Novartis-funded →
• Science Translational Medicine · Mannick et al. (2018)264-person Phase 2a: low-dose RTB101 plus everolimus reduced reported infections; everolimus alone a non-significant trend →
• resTORbio (2019-11-15)Phase 3 PROTECTOR 1 of RTB101 did not meet its primary endpoint; respiratory programme halted →
• ClinicalTrials.gov · NCT04668352PROTECTOR 1 registration: 1,024 enrolled, adults 65+ →
• ClinicalTrials.gov · NCT05835999EVERLAST: everolimus 0.5 mg daily or 5 mg weekly for 24 weeks, 106 adults, completed July 2026 →
• ClinicalTrials.gov · NCT06658093RESTOR: 194 adults 65-90, dose-finding then daily vs weekly vs placebo, primary completion July 2028 →
• ClinicalTrials.gov · NCT05949658Safer mTOR inhibition for human geroprotection: sirolimus vs everolimus, 72 adults, to March 2027 →
• Nature · Harrison et al. (2009)Rapamycin fed from 600 days extended mouse lifespan by 9% (males) and 14% (females) →
• FDA · Drugs@FDARapamune (sirolimus) approval history and current label, NDA 021083 →