Compound · fisetin
T2senolytics_antiaging

Fisetin

Flavonoid polyphenol found in strawberries, apples, and persimmons. Functions as a senolytic by inhibiting the PI3K/AKT/mTOR survival pathway and BCL-2/BCL-XL anti-apoptotic proteins in senescent cells, selectively inducing apoptosis without affecting healthy cells. Also activates SIRT1, reduces NF-kB-driven inflammatory signaling, and functions as a direct free radical scavenger.

Half-life
~2 hours
Bioavailability
~25-30% (oral, lipophilic, improved with fat)
Route
oral
Evidence tier
T2 — Single-RCT or mechanistic
Optimization pillars
anti-aging · cellular-health
References
4 peer-reviewed
Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative
100 mg/day
Daily antioxidant maintenance
moderate
500 mg/day
Intermittent senolytic (monthly)
aggressive
1500 mg for 2 consecutive days/month
Senolytic cycling protocol
Monitoring
  • hs-crp
  • fasting-glucose
  • hba1c
  • lipid-panel
  • alt
  • ast
  • creatinine
  • wbc
Contraindications
  • active-chemotherapy
  • severe-hepatic-impairment
  • pregnancy
  • concurrent-anticoagulants
References
  • PMID:29988130Fisetin is a senotherapeutic that extends health and lifespanEBioMedicine, 2018
  • PMID:30279143Senolytic drugs: from discovery to translationJ Intern Med, 2018
  • PMID:33271060Fisetin for COVID-19 in skilled nursing facilities (FLITE)ClinicalTrials.gov (NCT04537299), 2020
  • PMID:35277680Fisetin reduces markers of senescence in humans (AFFIRM-LITE)EBioMedicine, 2022
Notes

Fisetin is the most accessible senolytic on the planet. A strawberry extract that selectively kills zombie cells. The Mayo Clinic data is what elevated this from flavonoid obscurity to longevity protocol staple — Dr. James Kirkland demonstrated that acute high-dose fisetin (20mg/kg in mice) cleared senescent cells and extended healthspan. The human translational dose lands around 1500mg for two consecutive days per month. The daily low-dose approach is antioxidant, not senolytic. The distinction matters. You need acute high-dose exposure to trigger apoptosis in senescent cells.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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