{ "checked": "2026-10-25", "page": "https://jabbitapp.com/research/rapamycin-sirolimus-longevity-anti-aging-evidence-teardown.html", "fda_label": { "name": "Sirolimus tablets (generic of RAPAMUNE), Glenmark", "setid": "57fb4d90-3ccb-4a69-af1e-53be83f7a504", "effective": "2026-01-28", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57fb4d90-3ccb-4a69-af1e-53be83f7a504", "quotes": [ "WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS", "Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression", "Sirolimus tablets are indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants.", "Sirolimus tablets are indicated for the treatment of patients with lymphangioleiomyomatosis (LAM).", "Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections such as tuberculosis, fatal infections, and sepsis.", "There have been reports of impaired or delayed wound healing in patients receiving sirolimus", "Increased serum cholesterol and triglycerides requiring treatment occurred more frequently in patients treated with sirolimus", "Patients on immunosuppressive therapy are at increased risk for skin cancer.", "The use of live vaccines should be avoided during treatment with sirolimus", "Because grapefruit juice inhibits the CYP3A4-mediated metabolism of sirolimus, it must not be taken with or be used for dilution of sirolimus", "sirolimus can cause fetal harm when administered to a pregnant woman", "Azoospermia or oligospermia may be observed", "Cases of interstitial lung disease (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis), some fatal", "stomatitis, diarrhea, abdominal pain, nausea, nasopharyngitis, acne, chest pain, peripheral edema", "hypophosphatemia, hyperglycemia, diabetes mellitus" ] }, "hyftor_label": { "setid": "edb3ea90-5adc-48ec-99f5-ab963e302f18", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=edb3ea90-5adc-48ec-99f5-ab963e302f18", "quote": "HYFTOR is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older." }, "drugsfda": { "applications": 16, "anda": 11, "nda": { "NDA021083": "RAPAMUNE oral solution, 1999-09-15", "NDA021110": "RAPAMUNE tablets, 2000-08-25", "NDA213312": "FYARRO IV, 2021-11-22", "NDA213478": "HYFTOR topical gel, 2022-03-22", "NDA218528": "SCOMARA topical cream, 2026-07-20" } }, "registry": { "clinicaltrials_gov_rapamycin_sirolimus_with_aging_terms": 83, "note": "Broad search; most records are transplant, cancer or stent studies. We did not classify them all.", "selected": { "NCT04488601": [ "COMPLETED", 129, "AgelessRx" ], "NCT06550271": [ "COMPLETED", 67, "AgelessRx" ], "NCT07475546": [ "ACTIVE_NOT_RECRUITING", 30, "AgelessRx" ], "NCT06658093": [ "RECRUITING", 194, "The University of Texas Health Science Center at San Antonio" ], "NCT04629495": [ "ACTIVE_NOT_RECRUITING", 40, "The University of Texas Health Science Center at San Antonio" ], "NCT05835999": [ "COMPLETED", 106, "University of Wisconsin, Madison" ], "NCT04200911": [ "COMPLETED", 10, "The University of Texas Health Science Center at San Antonio" ], "NCT06022068": [ "COMPLETED", 14, "Karolinska Institutet" ], "NCT03373903": [ "ACTIVE_NOT_RECRUITING", 652, "Restorbio Inc." ], "NCT04139915": [ "WITHDRAWN", 0, "Restorbio Inc." ], "NCT05237687": [ "RECRUITING", 10, "Irina Timofte" ], "NCT07728175": [ "RECRUITING", 225, "University of Missouri-Columbia" ] } }, "pubmed": { "query": "(rapamycin[tiab] OR sirolimus[tiab]) AND (aging[tiab] OR ageing[tiab] OR longevity[tiab] OR healthspan[tiab] OR lifespan[tiab]) AND randomized controlled trial[pt]", "count": 18, "idlist": [ "41985884", "40188830", "35914953", "33977284", "33888596", "31761958", "31095313", "30932134", "29997249", "29408453", "28732480", "28482746", "28374166", "27798330", "25540326", "25332468", "22859389", "20150565" ], "human_trials_of_rapamycin_type_drugs_for_aging_outcomes": [ "25540326", "29408453", "29997249", "31761958", "33977284", "40188830", "41985884" ], "note": "The other records are dog, mouse, nutrition or exercise-signaling studies, or other drugs." }, "utsa_release": { "url": "https://news.utsa.edu/2026/03/large-rapamycin-clinical-trial-launches-at-ut-health-san-antonio/", "published": "2026-03-16", "quotes": [ "It is a randomized, placebo-controlled clinical trial involving approximately 84 older adults", "Rapamycin is widely discussed in popular culture as a longevity drug", "But there’s a difference between something that is biologically plausible and something that has been rigorously tested in people.", "Some individuals are experimenting with the drug on their own, often without medical supervision or reliable information about dosing or risks." ] }, "key_trials": [ { "trial": "RTB101 phase 3, 2021 (related drug)", "n": 1024, "result": "Main goal not met", "pmid": "33977284" }, { "trial": "RTB101 phase 2b, 2021 (related drug)", "n": 652, "result": "First analysis missed; pooled analysis hit", "pmid": "33977284" }, { "trial": "Phase 2a, 2018 (two related drugs)", "n": 264, "result": "Fewer infections reported", "pmid": "29997249" }, { "trial": "PEARL, 2025 (registry count)", "n": 129, "result": "Main goal not met; some gains in women", "pmid": "40188830" }, { "trial": "RAPA-EX-01, 2026", "n": 40, "result": "No benefit; may blunt exercise gains", "pmid": "41985884" }, { "trial": "Topical skin cream, 2019", "n": 36, "result": "Skin aging markers improved", "pmid": "31761958" }, { "trial": "Older-adult safety pilot, 2018", "n": 25, "result": "No clear changes; red-cell dips", "pmid": "29408453" } ], "key_trials_total_n": 2170, "abstract_quotes": { "1102508": { "title": "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle", "journal": "J Antibiot (Tokyo)", "year": "1975", "quotes": [ "A streptomycete was isolated from an Easter Island soil sample", "isolated in crystalline form and named rapamycin" ] }, "19587680": { "title": "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice", "journal": "Nature", "year": "2009", "quotes": [ "extends lifespan in invertebrates, including yeast, nematodes and fruitflies", "rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age", "On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males.", "The effect was seen at three independent test sites in genetically heterogeneous mice", "Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both." ] }, "24341993": { "title": "Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction", "journal": "Aging Cell", "year": "2014", "quotes": [ "Rapamycin increased lifespan more in females than in males at each dose evaluated" ] }, "27549339": { "title": "Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice", "journal": "Elife", "year": "2016", "quotes": [ "3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice", "a striking shift in cancer prevalence toward aggressive hematopoietic cancers" ] }, "25540326": { "title": "mTOR inhibition improves immune function in the elderly", "journal": "Sci Transl Med", "year": "2014", "quotes": [ "RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated.", "These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly." ] }, "29997249": { "title": "TORC1 inhibition enhances immune function and reduces infections in the elderly", "journal": "Sci Transl Med", "year": "2018", "quotes": [ "264 elderly subjects given the study drugs for 6 weeks", "was safe and was associated with a significant (P = 0.001) decrease in the rate of infections reported by elderly subjects for a year after study drug initiation" ] }, "33977284": { "title": "Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials", "journal": "Lancet Healthy Longev", "year": "2021", "quotes": [ "we recruited 652 participants in total", "we enrolled 1024 patients", "did not meet statistical significance but, in our second prespecified analysis, which included data from part 1 and part 2, we found a statistically significant reduction in the proportion of patients who had one or more laboratory-confirmed RTIs", "RTB101 did not reduce the proportion of patients with clinically symptomatic respiratory illness", "The study drug was found to be safe and well-tolerated across trials and treatment groups.", "In both trials, significantly more IFN-induced antiviral genes were upregulated in patients treated with RTB101 as compared with placebo" ] }, "29408453": { "title": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects", "journal": "Exp Gerontol", "year": "2018", "quotes": [ "placebo-controlled pilot study in 25 generally healthy older adults (aged 70-95 years)", "these were limited to facial rash (1 subject), stomatitis (1 subject) and gastrointestinal issues (2 subjects)", "statistically significant decrements in several erythrocyte parameters including hemoglobin (HgB) and hematocrit (Hct)", "no changes were noted in any other clinical laboratory, cognitive, physical performance, or self-perceived health status measure over the study period", "the OGTTs revealed no RAPA-induced change in blood glucose concentration, insulin secretion, and insulin sensitivity" ] }, "40188830": { "title": "Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results", "journal": "Aging (Albany NY)", "year": "2025", "quotes": [ "This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601)", "The primary outcome measure was visceral adiposity (by DXA scan)", "Adverse and serious adverse events were similar across all groups.", "and was associated with significant improvements in lean tissue mass and pain in women", "Visceral adiposity did not change significantly", "Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults", "Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy." ] }, "41985884": { "title": "Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial", "journal": "J Cachexia Sarcopenia Muscle", "year": "2026", "quotes": [ "40 sedentary adults aged 65-85 years", "Both groups improved chair-stand performance.", "Sensitivity analyses favoured placebo and reached statistical significance", "Seventeen participants (85%) in each arm reported ≥ 1 adverse event, but the total burden was higher with sirolimus (99 vs. 63 events), including one possibly drug-related serious adverse event (pneumonia).", "in sensitivity analyses, it may have modestly attenuated short-term functional improvements from a home exercise programme in older adults" ] }, "40394335": { "title": "Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial", "journal": "Commun Med (Lond)", "year": "2025", "quotes": [ "single-site open-label phase 1 clinical trial", "In ten participants (mean age 74 ± 4 years, 60% female), we find that rapamycin is not detectable in the CSF before or after treatment.", "systolic blood pressure and hemoglobin A1c increase, multiple erythrocyte parameters decrease, and there are no significant cognitive changes", "several Alzheimer's disease and inflammatory biomarkers increase after treatment" ] }, "41046300": { "title": "Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease", "journal": "Geroscience", "year": "2026", "quotes": [ "the pharmacokinetic properties of weekly oral rapamycin in 13 patients with early-stage AD", "Blood concentrations at Cmin were below immunosuppressive levels in all participants." ] }, "40971115": { "title": "Short-term mTOR inhibition by rapamycin improves cardiac and endothelial function in older men: a proof-of concept pilot study", "journal": "Geroscience", "year": "2026", "quotes": [ "the open-label study", "In all 6 subjects, transmitral blood flow, peak flow rate, and maximal blood acceleration showed statistically significant improvements while endothelial function also improved", "support future placebo-controlled studies in larger cohorts" ] }, "31761958": { "title": "Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial", "journal": "Geroscience", "year": "2019", "quotes": [ "Thirty-six participants were enrolled in the study, and nineteen discontinued or were lost to follow-up.", "A significant (P = 0.008) reduction in p16INK4A protein levels and an increase in collagen VII protein levels (P = 0.0077) were observed" ] }, "38310895": { "title": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review", "journal": "Lancet Healthy Longev", "year": "2024", "quotes": [ "resulting in 19 included studies", "Overall, no significant effects on the endocrine, muscular, or neurological systems were found.", "No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related diseases.", "Future studies should assess the remaining unexamined systems and test the effects of long-term exposure to rapamycin and its derivatives." ] }, "39951177": { "title": "Test of Rapamycin in Aging Dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the Dog Aging Project", "journal": "Geroscience", "year": "2025", "quotes": [ "The Test of Rapamycin In Aging Dogs (TRIAD) randomized clinical trial is a parallel-group, double-masked, randomized, placebo-controlled, multicenter trial", "the first rigorous test of a pharmacologic intervention against biological aging with lifespan and healthspan metrics as endpoints to be performed outside of the laboratory in any species" ] }, "28374166": { "title": "A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs", "journal": "Geroscience", "year": "2017", "quotes": [ "24 middle-aged healthy dogs", "Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo." ] }, "27883166": { "title": "Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study", "journal": "J Frailty Aging", "year": "2016", "quotes": [ "13 patients;", "elderly undergoing cardiac rehabilitation (CR)", "no improvement in frailty with rapamycin was noted" ] } }, "conflict_statements": { "33977284": "were employees of, and had equity in, resTORbio who manufactured RTB101", "40188830": "are employees and shareholders of AgelessRx", "39951177": "MK is a scientific advisor for TriviumVet" }, "title_only": { "42759606": { "title": "Rapamycin in Frail Older Subjects with Heart Failure with Preserved Ejection Fraction", "journal": "Mayo Clin Proc", "year": "2026" } }, "analysis": { "note": "Jabbit analysis. Rapamycin (sirolimus) is an FDA-approved immunosuppressant with a boxed warning, approved for kidney-transplant rejection prevention and LAM. It extends lifespan in mice, but no human trial has tested lifespan; the human aging trials are small or short, used surrogate measures, and gave mixed results, and the largest trials tested related drugs rather than rapamycin itself." } }