Fisetin

The strongest senolytic candidate from natural compounds in mouse studies. Human trials are underway but not yet published. High interest in the longevity community.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Mayo Clinic rodent studies (Yousefzadeh et al. 2018) showed lifespan extension and reduced senescence markers. The AFFIRM trial (human) is ongoing. Bioavailability is poor and likely requires high intermittent dosing. Senolytic effects appear dose-dependent.

• Potent senolytic in preclinical screens
• Lifespan extension in mouse models
• Reduces senescence-associated markers in animal tissues

100–500 mg/day for general antioxidant use. Senolytic protocols use higher intermittent doses (e.g. 20 mg/kg for 2 consecutive days monthly), but this is not validated in humans.

• GI discomfort at high doses
• Unknown long-term effects of senolytic dosing

Optimal human dosing and safety at senolytic doses are unknown. Bioavailability is a major limitation.

Mouse senolytic doses are very high relative to dietary intake. Human trial results are pending. Bioavailability may limit translation.

• Longevity48