The evidence base for fisetin
Fisetin is a flavonoid — a small plant molecule found in strawberries, apples, and onions — that has drawn scientific attention as a candidate senolytic. Senolytics selectively clear senescent cells, the aged and dysfunctional cells that accumulate with time and contribute to age-related disease. The fisetin evidence base spans mechanistic in vitro work, preclinical animal studies, and a small but growing set of human clinical trials.
Evidence at a glance
Bioavailability
Cardiovascular
Cellular senescence
Fisetin is a senotherapeutic that extends health and lifespan
Preclinical mouse study across two models (Ercc1⁻/Δ progeroid and aged wild-type C57BL/6:FVB) with in vitro senolytic screening. Mechanistic depth is strong, but there is no direct human evidence in this paper.
Tier 2Fisetin as a senotherapeutic agent — evidence and perspectives for age-related diseases
Comprehensive narrative review synthesising in vitro evidence, animal model data, and results from published and ongoing phase I/II human clinical trials. Not primary data, but the most complete evidence assessment available in the fisetin senotherapeutic literature.
Tier 4Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era
This article outlines the hypothesis and study protocol for an ongoing Phase II clinical trial, rather than presenting completed clinical efficacy data.
Tier 4Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection
This article is a literature review combined with computational (in silico) predictions of pharmacokinetics and toxicity, providing early mechanistic and hypothesis-generating evidence.
Tier 4New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463
This study provides early mechanistic in vitro evidence demonstrating the senolytic properties of fisetin and specific BCL-XL inhibitors in targeted human cell lines.
Tier 4Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect
Tier 4 reflects the in vitro-only design on two human lung cell lines, without animal or human data. The paper is nonetheless editorially important because it documents a senomorphic — not senolytic — mechanism for fisetin at concentrations spanning 1.25 to 160 μM in doxorubicin-induced senescent cells, directly contradicting the prevailing classification of fisetin as a senolytic. Publisher context: International Journal of Molecular Sciences is an open-access MDPI journal; MDPI's editorial practices have attracted criticism in some quarters, though this specific paper reports mechanistic in vitro work with a coherent method section and internally consistent data.