Fisetin

The 5.5 Neutral score reflects a real mechanism with thin and partly negative human translation. Fisetin is worth a structured 3-cycle trial for older adults with documented inflammatory load who already have sleep, training, and protein dialed in. It is not worth running as a daily longevity supplement for younger biohackers chasing healthspan; the Lee 2024 epigenetic-acceleration signal in adjacent senolytic class is a yellow flag until replicated. The Mayo AFFIRM-LITE primary results, when published, will likely move this score by 1 to 2 points in either direction. Bioavailability matters: use lipo or phytosomal formulations or skip the protocol.

✅ Best for: Older adults (50 plus) with documented inflammatory or metabolic load (elevated hs-CRP, joint stiffness, slow recovery, HbA1c drift) who already have the fundamentals locked in. Practitioners running structured 3-cycle trials with paired hs-CRP, ALT, and platelet biomarkers before and after. Users stacking fisetin with quercetin for senolytic class diversity on pulse days. People testing N-of-1 response over 6 to 12 months with qualitative readouts (Pulse Energy, Recovery Quality, Joint Comfort) rather than expecting acute effects. Geroscience-curious users who want exposure to the senolytic class but lack prescription access to dasatinib. The common thread is older, inflamed, fundamentals-first, and willing to track over months.

❌ Avoid if: Younger than 40 without documented inflammatory load; the Lee 2024 epigenetic-age-acceleration signal in dasatinib-quercetin users is a yellow flag for young senolytic users until replicated. On active chemotherapy without oncologist clearance, because senolytic interference with chemotherapy-induced senescence-as-tumor-suppressor is unmapped. On anticoagulants (warfarin, DOACs) or anti-platelet drugs (aspirin, clopidogrel, ticagrelor) without supervision; fisetin has measurable anti-platelet activity. Pregnant or breastfeeding (no safety data). On CYP2C9-sensitive medications (phenytoin, fluvastatin, losartan, sulfonylureas) or CYP1A2-sensitive medications (clozapine, theophylline). Active GI distress or recent surgery. Anyone using cheap unverified Cotinus coggygria extract instead of Novusetin or HPLC-verified lipo product.