Yousefzadeh · EBioMedicine 2018 · In vitro screening, ex vivo explant, and in vivo animal study · n=?

Fisetin is a senotherapeutic that extends health and lifespan.

Cited 1016 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical in vitro, ex vivo, and animal study with no clinical human trial data.

PubMed 30279143 · doi:10.1016/j.ebiom.2018.09.015 · record verified 2026-08-29

What was done

Researchers screened a panel of 10 flavonoid polyphenols for senolytic activity using oxidative stress-induced senescent murine fibroblasts and genotoxic stress-induced senescent human fibroblasts. The most potent compound, fisetin, was evaluated in progeroid mice (p16^INK4a-luciferase reporter) and aged wild-type mice via acute or intermittent administration to assess senescence markers, age-related histopathology, health span, and lifespan. Translation was tested ex vivo using human adipose tissue explants.

What was found

Fisetin showed the strongest senolytic activity among the 10 flavonoids tested. Acute or intermittent fisetin treatment reduced senescence markers in multiple tissues of progeroid and old mice and in specific cell subsets of murine and human adipose tissue. Late-life treatment in wild-type mice restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. The abstract provided no specific numerical values, lifespan extension percentages, or statistical metrics.

Why it matters

The findings identify fisetin as a potent natural senolytic capable of clearing senescent cells and extending lifespan in mice, supporting further investigation into senotherapeutic strategies for aging.

Limits

The study is entirely preclinical, relying on cell culture, ex vivo tissue explants, and mouse models, which cannot establish efficacy, safety, or dosing in humans. The abstract does not report sample sizes, quantitative effect sizes, survival data, or potential adverse effects.

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