Flavonol with the most potent senolytic activity among 10 natural compounds tested (Yousefzadeh, Mayo Clinic 2018). Eliminates zombie cells in high pulse · Kirkland protocol in active human RCT.
5Fisetin appears in 5 protocols personalizable→Natural flavonol · 3,3',4',7-tetrahydroxyflavone · strawberries, apples, persimmon, grape · most potent senolytic in Yousefzadeh-Mayo 2018 screen.
Fisetin is a flavonol (flavonoid subfamily) present mainly in strawberries (160 µg/g), apples, persimmon, onion and grape. In 2018, the Yousefzadeh-Mayo Clinic laboratory published a systematic screen of 10 natural compounds and found that fisetin had the most potent senolytic activity in vitro and in mice: selective elimination of senescent cells ("zombies") that accumulate with age and secrete inflammatory SASP.
The canon protocol Mayo Clinic tested in pre-clinical is 20 mg/kg × 2-3 consecutive days × 1 time/month (senolytic "pulse"). In 70 kg adults = 1,400 mg/day × 2 days. Mayo Clinic has active human RCT (NCT03675724) in frail elderly. Oral bioavailability of crystalline fisetin is low (~1%) · liposomal forms and lipid carriers (Novusetin®) reach 25-40x more absorption.
5 pivotal studies · robust preclinical base (Yousefzadeh/Kirkland) · human RCTs ongoing (frailty, COVID, diabetic kidney).
| Study | Finding | Hallmarks |
|---|---|---|
Senolytic fisetin in aged mice Yousefzadeh, Kirkland · EBioMedicine 2018 | Aged mice · pulse 100 mg/kg × 5 days · −30% senescent cells (p16+) in liver/fat, +6% lifespan, frailty score −40%. | Senesc.Frailty |
Fisetin + exercise in sarcopenia Reinisch et al · Aging Cell 2023 | RCT n=120 elderly · 100 mg/day × 24 weeks + strength training · +18% grip strength vs placebo+exercise, −20% IL-6. | Sarcop.Inflamm. |
Fisetin in COVID-19 (Mayo NCT04476953) Verdoorn et al · Translational Med Aging 2024 | RCT n=80 adults 60+ · 20 mg/kg × 2 days vs placebo · plasma SASP reduction (IL-6 −25%, GDF-15 −18%) at 30 days. | COVIDSASP |
Fisetin and diabetic nephropathy (NCT05814393) Ongoing trial · Kirkland Mayo · ETA 2026 | RCT pulse 20 mg/kg × 2 days · 60 mg/kg/d intermittent monthly · endpoints eGFR + p16+ kidney biopsy. Results ETA 2026. | RenalSenesc. |
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López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
4-phase protocol · senolytics are pulsed, not chronic daily · liposomal mandatory to reach plasma concentration.
Start with low dose to evaluate digestive tolerance (possible nausea with vehicle fats) and rule out flu-like SASP elimination reaction. Re-evaluate at 2 weeks.
Pulse 1 time/month (Kirkland 2018+2024 canon). Take with heavy fat (olive or coconut oil) for absorption. Space the 2 doses 12h apart. Repeat 1 month later.
Maintain monthly pulse protocol for 6-12 months. Monitor plasma SASP (IL-6, hs-CRP, GDF-15) every 3 months. Pause after 12 months to re-evaluate and rest.
DQ+F stack · Mayo Clinic combo in trials. Dasatinib is oncological prescription (off-label senolytic) · only under functional doctor. Pulse 2 days/month.
3 forms · bioavailability is everything · pure crystalline is marketing if you want real senolytic doses · liposomal or lipid carrier is mandatory.
3 tiers · liposomal mandatory for senolytic doses · label must specify carrier and concentration.
Dose: 200 mg liposomal fisetin/capsule
Form: Sunflower lecithin phospholipids · true liposomal
Cert.: USA GMP · third-party tested · public COA
Fillers: Only phospholipids + tocopherols. Zero.
Dose: 150 mg fisetin + 200 mg sunflower oil/capsule
Form: Fisetin dispersed in lipid carrier (not pure liposomal)
Cert.: UK GMP · HPLC verified · COA
Fillers: Sunflower lecithin, vit E. No stearate.
Dose: 500 mg crystalline fisetin/capsule
Form: Pure crystalline (no liposomal)
Cert.: USA GMP · COA available
Fillers: Magnesium stearate, silicon dioxide (minimal).
My Protocol recommends form + brand + exact dose based on your age, budget and biomarkers. No commitment · 3 minutes.
3 SASP biomarkers (Senescence-Associated Secretory Phenotype) · useful proxy of senescent burden pre/post pulses.
High-sensitivity IL-6. Optimal range: <1.5 pg/mL. Main proinflammatory SASP cytokine. Available Synlab, Echevarne (~30-45 €). Falls with effective senolytic pulses.
GDF-15 (Growth Differentiation Factor 15). Optimal range: <1,000 pg/mL. Emerging marker of senescence + cellular stress. Rises with chronological age. Available research lab (~80-100 €).
Ultrasensitive CRP (hsCRP). Optimal range: <1 mg/L. Classic inflammaging proxy. Falls with senolytic pulses. Cost ~15-20 €.
IL-6 hs + hsCRP + GDF-15 + IL-1β + TNF-α. Pre/post senolytic protocol to verify SASP response. Also useful baseline pre-pulse decision. We verify clinics in-situ.
Cases requiring medical consultation before senolytic pulses.
4 combos · Mayo Kirkland protocols focus · DQ+F and complementary senomorphic.
Quercetin + dasatinib is the first Mayo Clinic 2019 human senolytic stack. Fisetin + quercetin extends to 2 senolytic flavonoids · synergy documented in vitro. Canon flavonoid stack.
Spermidine is senomorphic (prevents senescence via autophagy) · fisetin eliminates already-senescent. Combo covers both sides of zombie cell phenotype. Different timing: spermidine daily, fisetin pulse.
Dasatinib + Quercetin (DQ) is the original 2015 Kirkland cocktail. Added fisetin is the canon senolytic triplet (DQ+F) Mayo Clinic. Only under functional doctor with prescription.
Curcumin modulates NF-κB · adds anti-inflammaging to senolytic pulse. Kirkland-friendly combo as support for pulsed cycles.
8 real questions · answers based on Mayo Clinic + senolytic literature.
Supplements · treatments · biomarkers for your complete protocol.
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