Fisetin
Mechanism, regulatory status, and an honest, tiered evidence map.
What it is
Class: Flavonoid senolytic / senotherapeutic
Also known as: 3,3',4',7-tetrahydroxyflavone
Relationship to senescence: A plant flavonoid identified as the most potent senolytic among a panel of flavonoids in preclinical screening; reduces senescence markers in multiple tissues via a hit-and-run mechanism.
Regulatory status
Sold as a dietary supplement; not an approved drug and not approved as a senolytic or for any longevity indication. Trial doses (e.g. 20 mg/kg/day for 2 days) far exceed typical supplement labelling and are used only under study protocols.
Mechanism
Reduces senescent-cell burden and SASP markers in aged/progeroid animal tissue; human trials target frailty and inflammation biomarkers. See /senolytics-vs-senomorphics.
Evidence — Mouse (wild-type, aged; progeroid models)
| Species / population | Aged wild-type mice and progeroid models. |
| Exposure, route, schedule | Intermittent/late-life oral fisetin. |
| Comparator / duration | Vehicle-treated age-matched controls. |
| Endpoint / numeric result | Reduced senescence markers across tissues; extended median and maximum lifespan when begun late in life (Yousefzadeh 2018). |
| What it did NOT establish | Mouse lifespan does not establish a human lifespan or healthspan effect. |
Evidence — Human (phase 2, ongoing) verify: primary source pending
| Species / population | Older adults with frailty/multimorbidity (AFFIRM / AFFIRM-LITE, older women and mixed cohorts). |
| Exposure, route, schedule | Oral fisetin 20 mg/kg/day for 2 days vs placebo (double-blind). |
| Comparator / duration | Placebo-controlled, randomized. |
| Endpoint / numeric result | Frailty (gait speed) and inflammatory markers — trial ongoing. |
| What it did NOT establish | No efficacy results are published; do not infer benefit from trial existence. |
Negative or null findings
- As of the search date, no peer-reviewed efficacy results from the human phase 2 fisetin trials had been published.