Systemic chronic inflammation contributes to the development of many age-related chronic diseases and represents a promising target for interventions aiming at promoting healthy aging. Fisetin is a naturally occurring flavonoid with anti-inflammatory, antioxidant and senolytic effects in vitro and in animal models, but evidence from randomised controlled trials in humans is limited. This study is a triple-blind, randomised, placebo-controlled trial designed to investigate the association between daily fisetin supplementation and changes in plasma soluble urokinase plasminogen activator receptor (suPAR) levels, as well as the occurrence and severity of adverse events, in generally healthy middle-aged and older adults, with exploratory evaluation of additional biomarkers and functional outcomes. Participants aged ≥ 50 will be randomised to receive 100 mg of oral fisetin or placebo once daily for 7 weeks. The primary outcome is the between-group difference in the change in plasma levels of suPAR from Baseline to Week 7. The secondary outcome is the between-group difference in the occurrence and severity of adverse events during the study period. In addition, exploratory outcomes will evaluate the association of fisetin supplementation with other soluble and cellular biomarkers of inflammation, aging and cellular senescence, as well as measures of frailty, physical and cognitive function and subjective health.
