Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ
Published in EBioMedicine
Abstract
Groundbreaking study identifying fisetin as a potent senolytic agent that selectively eliminates senescent cells. Demonstrated extension of healthspan and lifespan in progeroid mice with significant tissue-specific senescent cell clearance.
Methodology
Preclinical screening of ten flavonoids for senolytic activity in senescent murine and human cells, followed by in vivo testing in progeroid (Ercc1-/Delta) and naturally aged wild-type mice with intermittent oral fisetin dosing.
Key Findings
Fisetin was the most potent senolytic among the flavonoids tested, selectively killing senescent cells in culture. In progeroid and aged mice, intermittent fisetin reduced senescent cell burden across multiple tissues, lowered senescence-associated secretory phenotype markers and inflammation, improved tissue homeostasis, and extended both health span and median and maximum lifespan, even when started in late life.
Conclusions
Fisetin acts as a senolytic in mice and extends health span and lifespan when given intermittently, making it a leading candidate for human senolytic trials - which had not yet reported outcomes at publication.
Limitations
Preclinical only; no human efficacy data. Fisetin has poor oral bioavailability and rapid metabolism in humans, and mouse dosing (typically around 100 mg/kg intermittently) far exceeds ordinary supplement exposure. Lifespan extension in progeroid mice does not reliably predict effects in healthy humans.
Supplements Studied
Fisetin was the most potent senolytic of the flavonoids tested and extended median and maximum lifespan in aged mice.
Outcomes Measured
Fisetin identified as a potent senolytic agent that selectively eliminates senescent cells, demonstrating extension of healthspan and lifespan in progeroid mice with significant tissue-specific senescent cell clearance.
Study Details
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