Evidence Level
Fisetin's senolytic properties were established by Yousefzadeh et al. (2018) at the Mayo Clinic, who showed it was the most effective of 10 flavonoids tested at clearing senescent cells both in vitro and in vivo. The late-life lifespan extension in mice was particularly striking because it demonstrated benefit even when treatment began at advanced age. Currais et al. (2014) showed neuroprotective effects in Alzheimer's mouse models. The Mayo Clinic AFFIRM trial is testing fisetin in elderly women with frailty markers. Kirkland and colleagues have pioneered the senolytic field and consider fisetin among the most promising candidates alongside dasatinib+quercetin. The main limitation is poor oral bioavailability due to low water solubility, which liposomal formulations may address.