A summary of published research, not medical advice. See the Disclaimer.
Studies: every indexed trial and review on this topic, scored
Rapamycin (sirolimus) is an immunosuppressant that blocks mTOR, a protein complex that controls cell growth in response to nutrients. It and related drugs called rapalogs, such as everolimus, are used in transplant medicine and some cancers. Its longevity reputation comes from mouse studies. Human aging trials are small.
Best-supported effect: None for aging. No effect in healthy people reaches "Probably helps".
Most-cited weak claim: Slowing aging or extending lifespan in people. Unknown (very weak evidence).
How we grade evidence · Last reviewed: October 2026
What you need to know
No effect of rapamycin on aging in healthy people has more than weak evidence. It extended lifespan in mice, but no human study has measured lifespan. In the PEARL trial, healthy adults aged 50 to 85 on low weekly doses showed little or no difference in visceral fat or healthspan markers (weak evidence), and a phase 3 trial of the related drug RTB101 in adults 65 and older found little or no difference in respiratory illness (moderate evidence). Serious adverse events were not more common at low doses in healthy people. In patients on it or related drugs for disease, infections, higher cholesterol and triglycerides, and high blood glucose were more common (moderate evidence). It is approved as an immunosuppressant against organ transplant rejection, and longevity use is off-label. PEARL used 5 or 10 mg once weekly for 48 weeks.
No aging-related effect in healthy people meets the bar for this section. A 2024 systematic review of rapamycin and rapalogs for aging found 19 human studies, most small and short [1].
| Claim | Verdict | What was measured | Studied in |
|---|---|---|---|
| Fewer respiratory infections in older adults | Probably makes little or no difference (moderate evidence) One late-stage trial of RTB101, illness 26% vs 25% |
Hard outcome | Adults 65 and older, phase 3 |
| Less visceral fat, better healthspan markers | May make little or no difference (weak evidence) One 48-week trial where no one knew who got what, deep belly fat unchanged, other findings not repeated |
Lab marker | Healthy adults 50 to 85, PEARL trial |
Respiratory infections: A 2021 phase 3 trial gave the mTOR inhibitor RTB101 daily for 16 weeks of winter to about 1,000 adults aged 65 and older. Clinically symptomatic respiratory illness did not fall (26% vs 25%) [5]. Probably makes little or no difference (moderate evidence): one trial.
PEARL: This 48-week double-blind trial gave healthy, normally aging adults 5 mg or 10 mg compounded rapamycin weekly, or placebo. Visceral fat, the main outcome, did not change. Lean mass and pain improved in women on 10 mg, and some well-being scores improved on 5 mg. Nothing else changed [6]. May make little or no difference (weak evidence): the secondary findings were among many comparisons and need replication.
| Claim | Verdict | What was measured | Studied in |
|---|---|---|---|
| Longer lifespan | Unknown (very weak evidence) Mouse data only, no human study of lifespan |
Hard outcome | Mice |
| Better vaccine response in older adults | May help a little (weak evidence) Early-stage trials, mostly lab stand-in measures, infection benefit unconfirmed in late-stage testing |
Lab marker | Older adults, short courses of rapalogs |
| Skin aging | Unknown (very weak evidence) One exploratory trial applied to the skin, 19 of 36 dropped out |
Lab marker | 36 adults, topical, exploratory trial |
Lifespan: A 2009 study at three independent sites found rapamycin fed from 600 days of age extended median and maximum lifespan in genetically mixed mice of both sexes [2]. No human study has measured lifespan. Unknown (very weak evidence): mouse data only.
Vaccine response: In 2014, older volunteers given the rapalog everolimus (RAD001) had about a 20% greater antibody response to flu vaccine [3]. A 2018 phase 2a trial in 264 older adults found that a low-dose two-drug mTOR combination was followed by fewer reported infections over a year [4]. May help a little (weak evidence): early-phase trials, mostly surrogate outcomes, and a later phase 3 trial did not confirm fewer infections [5].
Skin: In an exploratory trial of topical rapamycin in people over 40 with sun-damaged skin, a marker of aging cells (p16) fell and collagen VII rose. 19 of 36 participants dropped out [7]. Unknown (very weak evidence).
Older adults: A 2018 pilot in 25 healthy people aged 70 to 95 on 1 mg/day found no changes in cognition, physical performance or glucose handling after at least 8 weeks [8].
Shown in humans
Shown only in animals or cells
Theory only
| Side effect | Verdict | How often vs placebo | Source | Studied in |
|---|---|---|---|---|
| Serious adverse events in healthy people at low doses | May not increase it (weak evidence) PEARL trial found similar rates across groups, none blamed on the drug |
No serious events attributed to the drug; similar rates across groups in PEARL | [1][6] | Healthy people |
| Lower hemoglobin and red cell counts | May happen (weak evidence) 25-person pilot study plus transplant data, anemia 23 to 33% vs 21% |
Small drops in a 25-person pilot; anemia 23 to 33% vs 21% in kidney transplant patients | [8][10] | Kidney transplant patients |
| Mouth sores | May happen (weak evidence) Equal counts in pilot study, no placebo rate in trial of LAM, a rare lung disease |
1 person vs 1 person in the pilot; stomatitis in at least 20% in the LAM trial (no placebo rate given) | [8][10] | |
| Infections | Probably happens (moderate evidence) Higher in people with aging-related diseases, no rate reported |
Higher in people with aging-related diseases; not reported as a rate | [1][10] | People with aging-related diseases |
| Higher cholesterol and triglycerides | Probably happens (moderate evidence) Kidney transplant data, high cholesterol 43 to 46% vs 23% |
High cholesterol 43 to 46% vs 23%; high triglycerides 45 to 57% vs 23% (kidney transplant) | [1][9][10] | Patients with solid tumors treated with everolimus |
| High blood glucose | Probably happens (moderate evidence) Pooled analysis of everolimus, a related drug, in solid tumors, 3.06 times the risk |
Risk ratio 3.06 (everolimus, solid tumors) | [9] | Patients with solid tumors treated with everolimus |
| Fatigue | Probably happens (moderate evidence) Pooled analysis of everolimus, a related drug, in solid tumors, 1.31 times the risk |
Risk ratio 1.31 (everolimus, solid tumors) | [9] | Patients with solid tumors treated with everolimus |
| Raised liver enzymes (ALT) | Probably happens (moderate evidence) Pooled analysis of everolimus, a related drug, in solid tumors, 2.96 times the risk |
Risk ratio 2.96 (everolimus, solid tumors) | [9] | Patients with solid tumors treated with everolimus |
| Low platelets | Probably happens (moderate evidence) Kidney transplant patients, 14 to 30% vs 9% |
14 to 30% vs 9% (kidney transplant) | [10] | Kidney transplant patients |
| Rash | Probably happens (moderate evidence) Kidney transplant patients, 10 to 20% vs 6% |
10 to 20% vs 6% (kidney transplant) | [10] | Kidney transplant patients |
| Joint pain | Probably happens (moderate evidence) Kidney transplant patients, 25 to 31% vs 18% |
25 to 31% vs 18% (kidney transplant) | [10] | Kidney transplant patients |
| Lymphoma and other cancers | Probably happens (moderate evidence) Lymphoma 0.7 to 3.2% vs 0.6 to 0.8% in kidney transplant patients |
Lymphoma 0.7 to 3.2% vs 0.6 to 0.8% (kidney transplant, vs azathioprine or placebo) | [10] | Kidney transplant patients |
| Protein in the urine, nephrotic syndrome | Probably happens (moderate evidence) Nephrotic syndrome (kidneys leak protein) 2.2% vs 0.4% against staying on a calcineurin anti-rejection drug |
Nephrotic syndrome 2.2% vs 0.4%; nephrotic-range protein 9.2% vs 3.7% (vs staying on a calcineurin inhibitor) | [10] | |
| Slow wound healing, lymphocele, fluid build-up | Probably happens (moderate evidence) Lymph fluid pockets (lymphocele) more common and dose-related, rates not reported |
Lymphocele more common and dose-related; rates not reported | [10] | |
| Lung inflammation (interstitial lung disease) | Unknown (very weak evidence) Reports of single patients only, from the drug label |
Case reports only | [10] | |
| Angioedema and other allergic reactions | Unknown (very weak evidence) Reports of single patients only, from the drug label |
Case reports only | [10] | |
| Low or absent sperm count | Unknown (very weak evidence) Reports of single patients only, reversible after stopping in most cases |
Case reports only; reversible after stopping in most cases | [10] | |
| Harm to a fetus | Unknown (very weak evidence) Animal studies only, per the drug label |
Animal data only | [10] |
Kidney transplant rates come from patients also on cyclosporine and corticosteroids at 2 or 5 mg daily, with side effects higher on 5 mg [10]. Longevity regimens use lower or weekly doses [6][8]. Rapamycin suppresses the immune system at transplant doses [8].
This lists what studies and labels report. A pharmacist or prescriber can say whether it applies to a specific person.
This lists what studies and labels report. A pharmacist or prescriber can say whether it applies to a specific person.
| Combined with | What happened | Verdict | Source | Studied in |
|---|---|---|---|---|
| Ketoconazole | Sirolimus exposure (AUC) rose 10.9-fold in healthy volunteers | May happen (weak evidence) Measured in healthy volunteers, sirolimus blood exposure up 10.9-fold |
[10] | Healthy volunteers |
| Erythromycin | Sirolimus AUC rose 4.2-fold; erythromycin AUC rose 1.7-fold | May happen (weak evidence) Sirolimus blood exposure up 4.2-fold, erythromycin blood exposure up 1.7-fold |
[10] | |
| Verapamil | Sirolimus AUC rose 2.2-fold; active verapamil rose 1.5-fold | May happen (weak evidence) Sirolimus blood exposure up 2.2-fold, active verapamil up 1.5-fold |
[10] | |
| Diltiazem | Sirolimus AUC rose 1.6-fold | May happen (weak evidence) Measured rise in sirolimus blood exposure of 1.6-fold |
[10] | |
| Rifampin | Sirolimus AUC fell about 82% | May happen (weak evidence) Measured fall in sirolimus blood exposure of about 82% |
[10] | |
| Cyclosporine, same time | Sirolimus AUC rose 148% (tablets); the rise was 33% when sirolimus was given 4 hours later | May happen (weak evidence) Sirolimus blood exposure up 148%, only 33% with 4-hour gap |
[10] | |
| Cyclosporine, long term | Higher creatinine and lower kidney filtration than controls in kidney transplant trials | Probably happens (moderate evidence) Transplant trials with comparison groups, higher creatinine (a kidney blood marker), lower kidney filtration |
[10] | |
| Statins or fibrates | Raised CPK (3%), muscle pain (6.7%) and rhabdomyolysis (under 1%) in transplant trials, no comparison group | Unknown (very weak evidence) Transplant trials reported rates, but no comparison group |
[10] | |
| Other CYP3A4 or P-gp inhibitors (e.g. fluconazole, clotrimazole, HIV and hepatitis C protease inhibitors, cimetidine) | The label states sirolimus levels could rise | Unknown (very weak evidence) Statement on the drug label only, no measurements listed for these drugs |
[10] | |
| Other CYP3A4 or P-gp inducers (carbamazepine, phenytoin, phenobarbital, St John's wort) | The label states sirolimus levels could fall | Unknown (very weak evidence) Statement on the drug label only, no measurements listed for these level-lowering drugs |
[10] | |
| Grapefruit juice | The label states it blocks sirolimus breakdown; no measured data given | Unknown (very weak evidence) Drug label says it blocks breakdown, no measured data given |
[10] | |
| Cannabidiol | The label states sirolimus levels may rise | Unknown (very weak evidence) Statement on the drug label only, no measurements listed for cannabidiol |
[10] | |
| ACE inhibitors | The label states the angioedema risk may increase | Unknown (very weak evidence) Statement on the drug label about risk of angioedema (sudden swelling), no rates listed |
[10] | |
| Calcineurin inhibitors (cyclosporine, tacrolimus) | The label states the risk of HUS/TTP/thrombotic microangiopathy may increase | Unknown (very weak evidence) Statement on the drug label about risk of HUS and TTP, rare blood clotting disorders, no rates listed |
[10] | |
| Acyclovir, atorvastatin, digoxin, glyburide, nifedipine, norgestrel/ethinyl estradiol, prednisolone | No clinically significant change in drug levels in interaction studies | May not increase it (weak evidence) Studies of taking both drugs together found no medically meaningful change in drug levels |
[10] |
These are the amounts used in the studies. They are not recommendations.
PEARL used 5 or 10 mg once weekly for 48 weeks [6]. The 2018 pilot used 1 mg daily for 8 weeks [8]. Immune trials used short courses of everolimus or RTB101 rather than rapamycin [3][4][5]. The skin trial used a topical preparation [7].
Sirolimus is FDA-approved as an immunosuppressant against organ transplant rejection [8]. It is not approved for aging or longevity. PEARL used compounded rapamycin [6], and longevity use is off-label.