Fisetin

01 What is Fisetin?

Fisetin is a flavonoid found in strawberries, apples, persimmons, and onions (though in very small amounts). It gained massive attention in 2018 when a Mayo Clinic study showed it was the most potent senolytic from a screen of 10 flavonoids — more effective than quercetin at clearing senescent cells in cell culture and extending lifespan in mice by 10% even when started in old age. That last point is critical. Most longevity interventions need to be started early to show benefit. Fisetin extended lifespan when given to mice that were already old — equivalent to starting treatment in a 75-year-old human. If this translates to humans (big if), it suggests fisetin could benefit people regardless of when they start taking it. The biohacking community has embraced fisetin enthusiastically, with many people doing periodic high-dose "senolytic flushes" (2-3 days of high-dose fisetin) combined with daily low-dose maintenance. The Mayo Clinic is currently running human clinical trials, which should provide definitive answers within a few years.

02 How Does It Work?

Fisetin acts as a senolytic by inhibiting multiple pro-survival pathways in senescent cells: PI3K/AKT, HIF-1alpha, and various anti-apoptotic BCL-2 family proteins. Senescent cells are dependent on these pathways for survival (they have activated the DNA damage response but not committed to apoptosis), so inhibiting them selectively kills senescent cells while sparing healthy ones. Beyond senolytics, fisetin is a potent antioxidant, reduces NF-kB-driven inflammation, inhibits mTOR (which may independently promote longevity), and supports neuronal health by reducing neuroinflammation and promoting neurotrophic factor expression.

03 What Does The Research Say?

The landmark 2018 EBioMedicine paper from the Mayo Clinic showed fisetin: was the most potent senolytic of 10 tested flavonoids, reduced senescent cell markers in aged mice, extended median and maximum lifespan by ~10%, and improved tissue function in old animals. Human trials are underway at the Mayo Clinic (AFFIRM-LITE for COVID long-haul, trials for frailty and osteoarthritis). Preliminary results are encouraging but not yet published in full. Bioavailability is a challenge (similar to quercetin) — liposomal formulations may improve this significantly.

04 Reported Dosages

Senolytic protocol: 1000-2000mg daily for 2-3 consecutive days, repeated monthly or every 2-3 months. Daily maintenance: 100-500mg daily. Mayo Clinic trial dose: 20mg/kg for 2 consecutive days. Bioavailability is poor — liposomal forms recommended. Legal supplement worldwide.

05 Side Effects & Risks

Very few reported side effects at standard doses. Mild GI discomfort at high senolytic doses. Theoretical concern: high-dose senolytics could transiently increase inflammation as senescent cells die and release their contents. Long-term safety data at senolytic doses is still being established.

06 Legal Status

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