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Everolimus (Afinitor / Zortress) — mTOR inhibitor (rapalog)
A rapamycin analog (rapalog, RAD001) approved as an oncology drug (Afinitor) and transplant immunosuppressant (Zortress). It is the mTOR inhibitor with the cleanest human geroscience signal: randomized trials in older adults showed it improved vaccine response and reduced infections — an immune-aging benefit, NOT demonstrated lifespan extension. A prescription immunosuppressant, not a supplement, and its later phase-3 respiratory-illness sibling trial missed its endpoint.
Prescription medication — not a dietary supplement
Everolimus is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Everolimus studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2008–2026 with a typical study size of 410 participants.
Based on 190 studies · 24 meta-analyses · 157 RCTs · 2,803 total participants
Confidence
High confidenceBy outcome
Everolimus is the mTOR inhibitor with the most directly relevant human geroscience data — randomized trials in older adults showing improved vaccine response and reduced infections (an immune-aging signal) — but no human trial shows it extends lifespan or healthspan, the program's larger confirmatory RTB101 phase-3 trial (PROTECT) missed its endpoint, and it is an immunosuppressant with real oncology-dose toxicities, so the longevity use stays emerging and off-label.
191 rigorous studies
160 randomized trials · 27 meta-analyses · 18 systematic reviews
Our evidence rating for Everolimus is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
162 trials ongoing or recruiting · 690 completed on ClinicalTrials.gov
300 of the completed trials have posted results
Registered trials show research momentum for Everolimus, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Everolimus (RAD001) is a semi-synthetic analog of rapamycin — a 'rapalog' — that, like rapamycin, binds FKBP12 and allosterically inhibits mTOR complex 1 (mTORC1), the central growth-signaling hub.
It is FDA-approved as an oncology agent (Afinitor: advanced renal cell carcinoma, hormone-receptor-positive breast cancer, neuroendocrine tumors, and TSC-associated lesions) and as a transplant immunosuppressant (Zortress), and it has the most directly relevant human data of any mTOR inhibitor for the geroscience hypothesis.
The reason everolimus matters to longevity is a small but influential set of randomized trials from the Mannick/Novartis program: in elderly volunteers, low-dose RAD001 enhanced the antibody response to influenza vaccination and reduced the exhaustion marker PD-1 on T cells (Sci Transl Med 2014); a follow-up combining a low dose of everolimus with the catalytic mTOR inhibitor BEZ235 (selective TORC1 inhibition) was associated with fewer infections and up-regulated antiviral gene expression over the following year (Sci Transl Med 2018).
These are the best human signals that mTOR inhibition can partially reverse immunosenescence.
The honest gap is large: there is NO human trial showing everolimus extends lifespan or healthspan, and the program's own larger confirmatory effort — the phase 2b/3 trials of the related mTOR inhibitor RTB101 (resTORbio) — failed, with the phase-3 PROTECT trial missing its primary endpoint of reducing clinically symptomatic respiratory illness in older adults.
So the immune-aging signal is real but unconfirmed at scale. Everolimus is also a genuine immunosuppressant with oncology-dose toxicities: stomatitis (mouth ulcers), non-infectious pneumonitis, infections, hyperglycemia and hyperlipidemia, and impaired wound healing.
Off-label longevity use is unproven, uses far lower/intermittent doses than the approved oncology regimen, and carries the same class risks as rapamycin plus everolimus-specific pneumonitis.
The score reflects a uniquely relevant — but small and unconfirmed — human immune-aging dataset against the absence of any lifespan outcome and real immunosuppressant risk.
Like rapamycin, everolimus binds FKBP12 and allosterically inhibits mTORC1, dampening anabolic/growth signaling — the basis of both its anti-tumor and proposed geroprotective effects.
Low-dose mTOR inhibition lowered exhaustion-marker PD-1 on T cells and enhanced vaccine response in older adults — a proposed mechanism for improved immune function with age.
Suppressed protein synthesis and cell growth underlie both the anti-proliferative oncology effect and the immunosuppression / impaired wound healing.
How Everolimus works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — mTOR inhibition is contraindicated in pregnancy.
Monitor glucose and lipids; mTOR inhibition can worsen both.
Hold around procedures — impaired wound healing and immunosuppression.
Caution — non-infectious pneumonitis is a known everolimus risk; report new respiratory symptoms.
Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit) sharply raise everolimus levels; inducers (rifampin) lower them. Dosing must account for this.
Immunosuppression can blunt vaccine response and makes live vaccines inadvisable during continuous dosing.
Additive immunosuppression and infection risk (relevant in transplant regimens).
Co-administration with ACE inhibitors increases the risk of angioedema.
Tip: Dose-related and often the dose-limiting toxicity; steroid mouthwash and lower/intermittent dosing reduce it.
Tip: Monitor glucose and lipids; more pronounced at oncology doses.
Tip: A characteristic everolimus toxicity — investigate new cough/dyspnea; may require dose reduction or discontinuation.
Tip: Monitor for infection; hold during acute illness or before surgery.
Everolimus has an evidence score of 4.2/10 — emerging evidence based on 18 indexed studies. A rapamycin analog (rapalog, RAD001) approved as an oncology drug (Afinitor) and transplant immunosuppressant (Zortress). It is the mTOR inhibitor with the cleanest human geroscience signal: randomized trials in older adults showed it improved vaccine response and reduced infections — an immune-aging benefit, NOT demonstrated lifespan extension. A prescription immunosuppressant, not a supplement, and its later phase-3 respiratory-illness sibling trial missed its endpoint. Representative study: PMID 35861940.
The commonly studied dose of Everolimus is No validated longevity dose. Geroscience trials used low intermittent dosing (e.g. ~0.5 mg/day or ~5 mg/week of RAD001) — unproven and not an approved regimen. Approved oncology dosing is 10 mg/day (Afinitor) and transplant dosing is trough-titrated (Zortress); both are far higher than any longevity protocol.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for Everolimus — consistent daily use matters more than the time of day. Take consistently with or without food (food lowers exposure).
Everolimus should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are stomatitis (mouth ulcers), hyperglycemia / hyperlipidemia, non-infectious pneumonitis. Use caution if any of these apply to you: Active infection; Pregnancy / breastfeeding; Significant immunosuppression or upcoming surgery (wound healing).
Beta-Glucans
Likely helpsPolysaccharides from yeast, mushrooms, or oats that train innate immune cells to respond faster to infections and pathogens.
Lactoferrin
Mostly mechanism / observationalA multifunctional iron-binding glycoprotein from milk with broad antimicrobial, anti-inflammatory, and immune-modulating properties.
Quercetin
Likely helpsFlavonoid with senolytic and anti-inflammatory properties — supports immune defense, allergy relief, and exercise performance.
Colostrum
Mostly mechanism / observationalFirst milk rich in immunoglobulins, growth factors, and antimicrobial compounds that supports gut health, immunity, and recovery.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 190 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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