What is Fisetin?
Fisetin is a naturally occurring flavonoid found in strawberries, apples, persimmons, onions, and cucumbers. While it has antioxidant properties, fisetin has gained attention primarily for its remarkable senolytic activity - the ability to selectively eliminate senescent cells.
Senescent cells, often called "zombie cells," are damaged cells that have stopped dividing but refuse to die. They accumulate with age and secrete inflammatory compounds (SASP) that damage surrounding healthy tissue, accelerating aging and disease.
In a landmark 2018 study at Mayo Clinic, fisetin was identified as the most potent natural senolytic compound tested, outperforming quercetin and other flavonoids in clearing senescent cells.
How Fisetin Works
Fisetin eliminates senescent cells by targeting their survival pathways. Senescent cells rely on anti-apoptotic (anti-death) pathways to survive. Fisetin disrupts these pathways, particularly the BCL-2 family of proteins, triggering apoptosis specifically in damaged cells.
Importantly, fisetin is selective - it targets senescent cells while leaving healthy cells unharmed. This specificity makes it safer than non-selective approaches to clearing damaged cells.
Fisetin's Key Actions
- Selectively eliminates senescent cells via BCL-2 pathway
- Reduces SASP inflammatory secretions
- Powerful antioxidant activity (10x more potent than quercetin)
- Crosses blood-brain barrier for neuroprotection
- Supports healthy immune function
Mayo Clinic Research
The 2018 EBioMedicine study by researchers at Mayo Clinic tested fisetin in aged mice and found remarkable results. Fisetin reduced senescent cell markers in multiple tissues, extended median lifespan, and improved physical function even when given late in life.
The study showed that fisetin treatment reduced inflammation, improved tissue function, and extended healthspan - the period of life spent in good health. These benefits occurred even when treatment started in old age, suggesting it's never too late to benefit.
Human clinical trials are now underway, including studies on COVID-19 recovery and age-related frailty, to validate these promising animal findings in humans.
Senolytic Protocol
Unlike daily supplements, senolytics are typically taken intermittently in higher doses to maximize senescent cell clearance. This "hit and run" approach allows the body to clear the targeted cells and then recover.
The Mayo Clinic mouse studies used the equivalent of roughly 20mg/kg body weight. For a 70kg human, this translates to approximately 1,400mg. However, human optimal dosing is still being researched.
Common Dosing Protocols
- Daily Antioxidant: 100-200mg per day continuously
- Monthly Senolytic: 500-1000mg daily for 2-3 consecutive days, once monthly
- Quarterly Protocol: 1000-1500mg daily for 2-3 days, every 3 months
- Best taken: With meals to improve absorption
Fisetin + Quercetin Synergy
Fisetin and quercetin work through complementary mechanisms and are often combined for enhanced senolytic effect. Quercetin is more affordable and inhibits HSP90, while fisetin is more potent and targets BCL-2 pathways.
The combination may provide broader senolytic coverage than either compound alone. The "Fisetin + Quercetin" protocol has become popular in the longevity community, typically taken together during senolytic dosing periods.
Life Extension's Senolytic Activator combines both compounds along with black tea theaflavins for a comprehensive approach to senescent cell clearance.
Safety and Considerations
Fisetin has been consumed safely in foods for centuries and is generally well-tolerated as a supplement. Clinical trials have not reported serious adverse effects at doses up to 1,400mg.
Potential interactions include blood thinners (fisetin may have mild anticoagulant effects) and certain medications metabolized by CYP enzymes. Consult a healthcare provider before starting high-dose senolytic protocols.
Some people report mild GI discomfort at higher doses. Taking with food typically resolves this issue.