Fisetin
Fisetin is a plant flavonoid (found in strawberries) studied for its ability to selectively clear senescent "zombie" cells in preclinical models, which made it one of the most closely watched senolytic candidates alongside dasatinib+quercetin. However, the human evidence has been mixed: a Mayo Clinic-led Phase 1/2 randomized, placebo-controlled trial in knee osteoarthritis (published in Osteoarthritis and Cartilage, 2025) using intermittent high-dose cycles found no significant improvement in pain, function, or cartilage health versus placebo, despite good safety and tolerability. Smaller pilot studies have shown fisetin can reduce circulating senescence and inflammatory (SASP) markers in older adults, and separate trials are underway in sepsis, long COVID, and peripheral artery disease. Given this gap between promising mechanistic/animal data and underwhelming early clinical outcomes, fisetin should be considered an investigational, not proven, longevity intervention at this time; discuss realistic expectations with your physician before use.
Mechanism of Action
Fisetin is proposed to act as a senolytic by selectively inducing apoptosis in senescent cells, which resist normal cell death and accumulate with age, secreting inflammatory factors known as the senescence-associated secretory phenotype (SASP). In vitro and animal studies suggest it works partly by inhibiting PI3K/AKT survival signaling that senescent cells rely on, alongside antioxidant and mild anti-inflammatory activity. Most of this mechanistic evidence comes from cell and animal models rather than confirmed human pharmacodynamics, and researchers have not established the exact dose or exposure needed to reproduce senolytic effects in people.
Dosing Protocol
100-500mg daily, or intermittent high-dose senolytic cycles (research protocols use ~20mg/kg for 2 consecutive days, repeated monthly)mg
Standard starting dose based on research
Therapeutic Range
100
Minimum
1500
Maximum
With a meal containing fat to aid absorption
Cycling Protocol
Some longevity practitioners and research protocols use intermittent 'hit-and-run' senolytic dosing (e.g., a large dose on 2 consecutive days, then weeks off) rather than daily use, based on the theory that senescent cells only need to be transiently targeted; this pattern was used in the Mayo Clinic knee osteoarthritis trial (3 cycles of 20mg/kg for 2 days, 28 days apart) but did not outperform placebo, so optimal human cycling is unproven.
Dosages are general guidelines. Individual requirements vary based on body weight, health status, and specific goals. Start with lower doses and adjust based on response.
Benefits
Primary Benefits
- Senescent cell clearance (preclinical)
- Reduction of inflammatory SASP markers
- Antioxidant support
- Cartilage/joint cell health (studied, not proven)
Secondary Benefits
Safety Information
Contraindications
Do not use if any of the following apply:
- •Pregnancy and breastfeeding (insufficient safety data)
- •Known bleeding disorders or anticoagulant use (theoretical antiplatelet effect at high doses)
- •Upcoming surgery
Drug/Supplement Interactions
May interact with the following. Consult a healthcare provider before combining:
Potential Side Effects
Some users may experience:
This is not a complete list of interactions or side effects. Individual responses vary. Always start with the lowest effective dose and monitor your response. Report any adverse effects to your healthcare provider.
Quality Markers
Look for these specific quality indicators when sourcing this compound:
- Third-party tested for purity/heavy metals
- Enhanced-bioavailability forms (liposomal or complexed) given fisetin's naturally poor oral absorption
- Standardized extract with verified fisetin content (not just fruit powder)
Trusted Certifications
Note: Supplement quality varies dramatically between brands. Cheap supplements often contain fillers, incorrect doses, or contaminants. Investing in quality products from reputable manufacturers is essential for safety and efficacy.
Evidence Profile
Evidence Score
4/10
Emerging/Anecdotal
Limited clinical data, primarily mechanistic studies or user reports
Evidence Scale
8-10
Strong
5-7
Moderate
1-4
Emerging
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