Fisetin

Fisetin is the most potent natural senolytic compound identified, achieving approximately 68% clearance of senescent cells in aged mouse tissues—comparable to genetic clearance methods, the 'ground truth' of senolytic efficacy (Buck Institute, PMC12341784) and outperforming the 52% clearance achieved by resveratrol (PMID: 29470326). This strawberry-derived polyphenol (~160 µg/g) works by inhibiting PI3K/Akt/mTOR and Bcl-2 family proteins, while also offering anti-inflammatory, antioxidant, and neuroprotective effects. Mayo Clinic screening ranks it among the most potent natural senolytics, with 2.5× the potency of NMN, another entry on this list. Its safety profile is more suitable for broad biohacker adoption than prescription-only dasatinib (not ranked here). Human data remain limited but promising: a COVID-19 elderly trial confirmed tolerability, and AFFIRM-LITE is analyzing efficacy. Fisetin also synergizes with quercetin for enhanced senolytic effect. Typical pulse protocols: 500–1500 mg/day for 2–3 consecutive days/month, taken with fat for bioavailability; liposomal/emulsified versions cost $30–60/month.