Fisetin

What it is

Fisetin is a flavonol found in strawberries, apples, persimmons, onions, and cucumbers. Pre-clinical work showed fisetin selectively kills senescent cells across multiple tissues and extended healthspan and median lifespan in aged mice when given in late life.

Why it’s of interest

In the Yousefzadeh et al. 2018 screen of candidate senotherapeutics, fisetin was the most potent and had a favourable safety profile relative to dasatinib-containing protocols. Several human trials are ongoing for frailty, post-COVID, and chronic kidney disease.

Mechanism

Fisetin targets multiple senescence-associated anti-apoptotic pathways (PI3K/AKT, p53, BCL-family) and may have separate anti-inflammatory and antioxidant effects.

Open questions

• Oral bioavailability is poor; the effective tissue concentration from typical supplement dosing is uncertain.
• Optimal protocol (intermittent “hit-and-run” vs daily) is unclear.
• Long-term human safety data are not available.

Practical use

Sold over the counter as a supplement. Common protocols draw from the mouse studies and use ~20 mg/kg for 2 consecutive days, repeated monthly — but this is extrapolation, not evidence-based dosing.

Related entries

Senolytics, Cellular senescence, Quercetin.