Fisetin
3,3',4',7-tetrahydroxyflavone
Overview
Fisetin is a flavonoid polyphenol found in strawberries, apples, and other fruits that has emerged as one of the most potent senolytic compounds identified — agents that selectively eliminate senescent cells ('zombie cells') that accumulate with aging and drive chronic inflammation. Research at the Mayo Clinic and the Buck Institute for Research on Aging has positioned fisetin as one of the leading senolytic candidates for clinical translation. Human clinical trials are underway for conditions including aging frailty, COVID-19 complications, Alzheimer's disease, and kidney disease, establishing fisetin as a frontline compound in the geroscience field.
Compound Data
Molecular Formula
C15H10O6
Molecular Weight
286.24 g/mol
IUPAC Name
2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one
PubChem CID
5281614Where does Fisetin sit?
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Mechanism of Action
Fisetin's primary senolytic mechanism involves inhibition of pro-survival pathways in senescent cells. Senescent cells abnormally upregulate anti-apoptotic proteins including BCL-2, BCL-XL, and PI3K/AKT that protect them from programmed cell death. Fisetin inhibits these pathways, selectively restoring apoptotic sensitivity in senescent cells while sparing normal healthy cells. Additionally fisetin activates sirtuin pathways, inhibits mTOR, and has potent antioxidant and anti-inflammatory activity through NF-κB inhibition and direct free radical scavenging. In animal models, intermittent high-dose fisetin treatment has reduced senescent cell burden, reduced inflammatory markers, and extended healthspan. Its ability to cross the blood-brain barrier also gives it potential neuroprotective applications.
Dosage Information
Typical Dose
20 mg/kg body weight (senolytic protocol, 2-3 days per month)
Frequency
Pulse dosing — 2-3 consecutive days per month for senolytic effect, or 100-500 mg daily for general antioxidant use
Administration
Oral capsule with fat for improved absorption
Notes
Senolytic protocols use intermittent high-dose approach rather than daily dosing. Human senolytic trials have used doses of 20mg/kg for 2 consecutive days. Fat co-administration significantly improves bioavailability.
Potential Side Effects
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Quick Facts
- Administration
- Oral capsule with fat for improved absorption
- Typical Dose
- 20 mg/kg body weight (senolytic protocol, 2-3 days per month)
- Frequency
- Pulse dosing — 2-3 consecutive days per month for senolytic effect, or 100-500 mg daily for general antioxidant use
- References
- 0 curated + 47 from PubMed
- Clinical Trials
- 6 registered
- Evidence Score
- 66.4 / 100