Fisetin

Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant polyphenol found in strawberries, apples, onions, and cucumbers — concentrated particularly in strawberries where it reaches approximately 160 micrograms per gram of fruit. Despite its humble dietary origins, fisetin has emerged as one of the most potent senolytic compounds identified, offering a safety profile that makes it uniquely suitable for broader biohacker adoption compared to the prescription-only dasatinib. The landmark preclinical evidence comes from Buck Institute research (PMC12341784) demonstrating that fisetin achieves approximately 68% clearance of senescent cells in aged mouse tissues — a magnitude comparable to genetic clearance methods that use inducible suicide genes to selectively eliminate p16- or p21-expressing cells. This comparison is significant: genetic clearance is considered the 'ground truth' of senolytic efficacy, and fisetin reaching equivalent clearance via a small-molecule flavonoid represents a remarkable result. Fisetin's senolytic mechanism operates through inhibition of pro-survival pathways in senescent cells — specifically the PI3K/Akt/mTOR axis and Bcl-2 family proteins — while also demonstrating anti-inflammatory, antioxidant, and neuroprotective activities. Mayo Clinic researchers have classified it as one of the most potent natural senolytics identified in systematic screening of plant compounds. Human clinical data for fisetin specifically remains limited — the most relevant trial examined it in COVID-19 elderly patients with favorable tolerability — but its safety profile in preclinical and early human studies is described universally as exceptional. A human senolytic efficacy trial (AFFIRM-LITE) has examined fisetin in older adults, with tolerability confirmed and efficacy signals under analysis. Typical senolytic protocols use fisetin at 500–1500mg/day for 2–3 consecutive days per month, mirroring the pulse-dosing rationale used for D+Q. Bioavailability is enhanced significantly by taking fisetin with fat-containing food. Formulations with enhanced bioavailability (liposomal or emulsified) are preferred given the compound's poor water solubility. Cost is modest — $30–60/month for quality pulse-dose protocols.