Fisetin
The most-studied natural senolytic — a compound that selectively kills senescent 'zombie' cells. Pulsed protocols are how it's usually run.
Animal data for senolytic effects is striking — extended healthspan, reduced age-related markers. Human trials are early-stage (Mayo Clinic AFFIRM-LITE, others ongoing). Neuroprotection evidence is moderate. The clinical case is more theoretical than proven so far, but plausible mechanism and excellent safety make it a reasonable bet in longevity stacks.
Fisetin is a flavonol found in strawberries, apples, and persimmons. Mayo Clinic research (Yousefzadeh et al., 2018) screened a library of flavonoids and identified fisetin as the most potent natural senolytic — meaning it selectively triggers apoptosis in senescent cells (damaged cells that have stopped dividing but secrete inflammatory signals, driving aging and chronic disease). The senolytic dose is high and pulsed (2 days per month or so), rather than daily — the idea being to clear senescent cells periodically rather than continuously. Also has standalone antioxidant and neuroprotective activity, and is used in some Alzheimer's research protocols.
- Form
- Fisetin capsules — usually 100–500 mg per serving. Liposomal or with-piperine for absorption (fisetin has poor bioavailability on its own).
- Dose
- Senolytic pulse: 1,000–1,500 mg/day for 2 consecutive days, repeated every 2–4 weeks. Daily low-dose: 100–200 mg/day for general antioxidant / neuroprotective use.
- Timing
- With food, especially fat-containing. Split high doses across the day.
- Schedule
- Pulsed (2 days, then 2–4 weeks off) for senolytic protocols. Daily for low-dose neuroprotection.
- Side effects
- Generally well-tolerated even at pulse doses. Mild GI upset, headache.
- Interactions
- Anticoagulants — mild additive. CYP enzyme substrates — possible interactions (limited data).
- Contraindications
- Pregnancy / lactation (no data). Active cancer / chemotherapy (discuss with oncologist — senolytics could theoretically interact). Bleeding disorders.
- Lab markers
- Not standard. Inflammatory markers (CRP, IL-6) and senescence biomarkers (p16INK4a) in research contexts.
- Food sources
- Strawberries (the richest dietary source), apples (with skin), persimmons, onions, grapes, cucumber. Even a strawberry-heavy day delivers only milligrams — therapeutic effect requires supplementation.
Pairs with
Quercetin (also a senolytic — often combined). Dasatinib + quercetin (the Kirkland senolytic protocol — Rx). Curcumin, EGCG (polyphenol synergy).
within Polyphenols & antioxidants