Fisetin & Senolytics: Clearing Zombie Cells

Cellular senescence is a stress response where damaged cells enter permanent arrest instead of apoptosis. They accumulate with age, secreting SASP (senescence-associated secretory phenotype) — inflammatory cytokines that damage neighboring tissue.

Senolytics selectively induce apoptosis in senescent cells while sparing healthy ones. The goal: periodic 'cleanup' pulses that reduce systemic inflammation and theoretically slow age-related decline.

Mayo Clinic screen: In 2018, researchers tested 10 flavonoids; fisetin showed the most potent senolytic activity in mouse tissue cultures. Oral fisetin reduced senescent cell burden and extended median and maximum lifespan in aged mice.

Human trials: Small Mayo Clinic pilot studies in diabetic kidney disease and osteoarthritis showed safety and biomarker improvements. A larger Alzheimer's trial is ongoing. No published human lifespan data exists.

Fisetin vs quercetin: Quercetin is cheaper and often combined with dasatinib in clinical protocols. Fisetin alone is the DIY biohacker approach — lower evidence bar but better safety profile than prescription combos.

Spermidine/urolithin A synergy: Senolytics clear zombie cells; autophagy activators (spermidine, urolithin A) improve cellular cleanup machinery. Some longevity stacks combine both.

Standard DIY pulse: 500mg fisetin twice daily (1000mg total) for 2 consecutive days. Repeat monthly or quarterly. Take with a fat-containing meal — fisetin is poorly absorbed otherwise.

Aggressive protocol (research-inspired): 20mg/kg/day for 2 days — roughly 1400mg for a 70kg adult. Used in some Mayo-inspired self-experiments. Start lower.

Quercetin add-on: Some add 500mg quercetin with each fisetin dose for synergistic senolytic effect. Evidence for the combo in humans is sparse.

What to avoid: Dasatinib + quercetin (D+Q) is the clinical gold standard but dasatinib is a prescription leukemia drug — not appropriate for unsupervised use.

During pulse: Some report mild fatigue or flu-like feeling — possibly die-off of senescent cells. Usually resolves within 48 hours.

Week after: Anecdotal reports of improved joint comfort, skin clarity, and energy. Highly variable and placebo-prone.

Long-term: Unknown. This is a bet on emerging science, not a proven intervention.

Experimental status: No long-term human safety data for high-dose pulsing. You're an early adopter, not a clinical trial participant (unless you enroll in one).

Drug interactions: Fisetin inhibits some CYP enzymes. Caution with chemotherapy, immunosuppressants, and blood thinners.

Pregnancy: Avoid — insufficient safety data.

Quality: Fisetin supplements vary wildly in purity. Use brands with third-party COA showing actual fisetin content.

r/longevity treats fisetin as the most accessible senolytic — above quercetin alone, below prescription D+Q protocols. 'Pulse monthly, don't daily dose' is universal advice.

Peter Attia is cautious: interesting preclinical data, insufficient human evidence for strong recommendation. DIY community proceeds anyway with informed consent to uncertainty.