Fisetin
Fisetin — Senolytic Flavonoid
What is Fisetin?
Fisetin is a naturally occurring flavonoid found in strawberries, apples, persimmons, and cucumbers. It has emerged as one of the most potent natural senolytics — compounds that selectively eliminate senescent cells (cells that have permanently stopped dividing but resist apoptosis and secrete inflammatory factors). Senescent cell accumulation drives aging and age-related disease; their elimination is a central strategy in the longevity field.
Fisetin induces apoptosis in senescent cells by inhibiting the PI3K/Akt survival pathway that senescent cells rely on — while leaving non-senescent cells unaffected (as they have normal apoptotic machinery). It also activates sirtuins through NAD+-dependent pathways, has potent anti-inflammatory effects via NF-kB inhibition, and crosses the blood-brain barrier to provide neuroprotection. The Mayo Clinic-led human trial (AFFIRM-LITE) tested fisetin for this senolytic application.
Research Evidence
The Mayo Clinic study in mice demonstrated fisetin reduced senescent cell burden, extended median and maximum lifespan, improved health markers, and restored cognitive function in aged animals.
Phase 2 AFFIRM-LITE trial confirmed fisetin safety in older adults at 20 mg/kg for 2 consecutive days. Biomarkers of senescence were reduced. Full efficacy results are being analyzed.
Fisetin consistently shows cognitive and anti-inflammatory benefits in animal models. Human cognitive data is limited to ongoing trials.
Evidence grades: Gold = RCT human data · Silver = consistent animal/human data · Bronze = limited or preliminary
Dosing Protocols
Reconstitution / Preparation
This compound does not require reconstitution — it is available as an oral or pre-mixed formulation.
Frequently Asked Questions
Is Fisetin the same as Quercetin?
Both are senolytic flavonoids — Quercetin is the most famous, Fisetin is newer but appears more potent in senolytic assays. The Mayo Clinic research identifies Fisetin as having stronger senolytic activity than Quercetin. Many longevity protocols combine both: Dasatinib + Quercetin (the original D+Q senolytic protocol) and Fisetin as an alternative or adjunct.
What are senescent cells and why do they matter?
Senescent cells are cells that have permanently stopped dividing (usually due to DNA damage, telomere shortening, or oxidative stress) but resist normal programmed cell death. They accumulate with age and secrete inflammatory factors (the SASP — senescence-associated secretory phenotype) that damage neighboring tissues. Reducing senescent cell burden is a key longevity strategy — the 'Hallmarks of Aging' framework identifies cellular senescence as one of the primary drivers of aging.
References
- [1]Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.
- [2]Verdoorn BP, Evans JL, Hanson GJ, et al. Fisetin for COVID-19 in skilled nursing facilities (AFFIRM-LITE). medRxiv 2021.
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This profile was prepared using AI-assisted research synthesis. Citations are provided where applicable — verify with primary sources before clinical application.
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