Fisetin (liposomal) — The Strawberry Senolytic

Fisetin is a naturally occurring flavonoid that acts as a potent senolytic, selectively inducing apoptosis in senescent cells by inhibiting anti-apoptotic pathways (such as the PI3K/AKT/mTOR and Bcl-2 pathways). It also functions as a strong antioxidant and anti-inflammatory agent, reducing the secretion of senescence-associated secretory phenotype (SASP) factors including IL-6 and TNF-α. Additionally, fisetin activates sirtuins (SIRT1) and AMPK, promoting cellular homeostasis and metabolic health.

Multiple clinical trials are underway (including at the Mayo Clinic) evaluating fisetin's senolytic effects in older adults, frailty, and osteoarthritis. Early pilot data suggests potential reductions in markers of inflammation and cellular senescence, but large-scale, peer-reviewed human longevity efficacy data remains limited. Animal studies show robust extension of healthspan and lifespan.

20 mg/kg/day for two consecutive days per month (the Mayo Clinic protocol) is the most widely studied senolytic dosing regimen in clinical trials. Some daily supplements use 100–500 mg/day for general antioxidant support. Liposomal formulations are often preferred due to fisetin's naturally poor oral bioavailability.

Fisetin is generally considered safe with a favorable toxicity profile in early human trials and extensive animal studies. Mild gastrointestinal discomfort (nausea, diarrhea) may occur at high doses. Due to its mechanism of action, long-term daily high-dose use is often avoided in favor of intermittent "hit-and-run" dosing to prevent potential interference with normal cellular repair processes. Safety in pregnancy and breastfeeding is unestablished.

Key Papers