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Fisetin

Senolytic flavonoid that may clear aged 'zombie' cells

What It Is

Fisetin is a plant flavonoid (concentrated in strawberries) identified by Mayo Clinic researchers as the most potent natural senolytic — a compound that selectively kills senescent cells. These 'zombie cells' accumulate with age and secrete inflammatory factors.

How It Works

Fisetin inhibits pro-survival pathways (PI3K/Akt, mTOR) in senescent cells, triggering apoptosis while sparing healthy cells. It also has anti-inflammatory and antioxidant properties. Some protocols use intermittent high-dose 'senolytic pulses.'

The Science

Fisetin is a senotherapeutic that extends health and lifespan

EBioMedicine (2018) · PubMed

Landmark mouse study from Mayo Clinic showing fisetin reduced senescent cell burden and extended lifespan even when given late in life.

Dosage

Senolytic protocol: 20mg/kg for 2 consecutive days per month (per mouse data, human dose ~1400mg for a 70kg person). Daily low-dose: 100–500mg. Optimal human dosing is NOT yet established.

Safety

Generally safe at low doses as a dietary flavonoid. High-dose senolytic protocols have limited human safety data. The Mayo Clinic AFFIRM trial is evaluating safety in humans. Caution with blood thinners.

Skeptic's Corner

This is perhaps the most exciting but also most preliminary product on our list. The senolytic data comes primarily from mouse studies. The AFFIRM-LITE human trial at Mayo Clinic is ongoing but results aren't published yet. Taking high-dose fisetin based on mouse data is a genuine gamble. We include it because the mechanism is compelling, but the evidence bar is barely met.

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