Fisetin
A plant flavonoid (found in strawberries) that emerged as one of the most potent natural senolytics in screening studies. It cleared senescent cells and extended lifespan in mice, and is used off-label in intermittent 'hit-and-run' senolytic protocols, but human outcome data are essentially absent and trials are ongoing.
01 Overview
Fisetin is a flavonol present in strawberries, apples, and other plants. In a 2018 screen it was the most effective natural senolytic tested, selectively killing senescent cells, and when given to aged mice it reduced senescent-cell markers and extended median and maximal lifespan even when started late in life.
Because senescent cells accumulate with age and drive chronic inflammation, fisetin is used in biohacking as an intermittent senolytic — high doses for a few consecutive days, repeated periodically — mirroring the 'hit-and-run' dosing tested in mice. Human trials (e.g. Mayo Clinic studies in frailty and inflammation) are underway but have not reported outcome benefits. Oral bioavailability is poor, prompting use of liposomal formulations.
02 Mechanism
Selectively induces apoptosis in senescent cells (senolysis), partly via inhibition of pro-survival pathways; also acts as an antioxidant and anti-inflammatory flavonoid.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Daily (low) | 100–200 mg/day | Oral | Low daily use as an antioxidant flavonoid. |
| Senolytic pulse | 1000–1500 mg/day | Oral | Intermittent high-dose protocol, e.g. 2-3 consecutive days monthly, mirroring mouse studies. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Senolysis (senescent-cell clearance)Selectively reduces senescent-cell burden in multiple mouse tissues. | significant in mice | Preclinical | |
| Lifespan extension (mice)Late-life fisetin extended lifespan and healthspan in one influential mouse study. | extended median/max in aged mice | Preclinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Generally well tolerated / limited human dataNo significant toxicity signals in short use, but human safety at senolytic doses is not established. | Mild | Uncharacterised | Unconfirmed | |
| Possible drug interactionsFlavonoids can inhibit CYP enzymes and affect drug transporters, a theoretical interaction risk at high doses. | Moderate | Uncommon | Preclinical |