A Danish triple-blind, randomised, placebo-controlled trial is testing whether 100 mg of oral fisetin daily for 7 weeks reduces plasma soluble urokinase plasminogen activator receptor (suPAR) — an established systemic inflammation marker linked to age-related disease risk — in generally healthy adults aged 50 and over. Secondary endpoints include adverse event profiling, while exploratory arms examine cellular senescence biomarkers, frailty indices, and cognitive and physical function measures.
Fisetin sits at an intriguing intersection of flavonoid biochemistry and geroscience. Its in-vitro and rodent data are compelling — particularly its senolytic activity clearing p21/p16-positive senescent cells — but human translation has lagged almost every other candidate in this space, including quercetin and dasatinib-navitinib combinations. Choosing suPAR as the primary endpoint is a shrewd design decision: suPAR is a robust, relatively stable pan-inflammatory glycoprotein that predicts all-cause mortality and multimorbidity better than CRP in population studies, giving this trial genuine mechanistic teeth.
Critically, this is a protocol paper — no efficacy data exist yet. The 100 mg dose is conservative; prior human pilot work used 20 mg/kg episodic dosing, making chronic low-dose comparison difficult. Seven weeks may be insufficient to detect senolytic remodeling. Still, the trial's rigorous blinding, biomarker breadth, and focus on the under-studied 50–65 age bracket make it an important infrastructure investment for the field. Confirmatory results would be incrementally significant; a positive suPAR signal would meaningfully accelerate fisetin's translational case.
