Clinical Translation of Fisetin for Age-Related Diseases: Current Evidence and Future Opportunities.

Fisetin, a naturally occurring flavonoid, has garnered interest as a potential intervention for age-related diseases due to its anti-inflammatory, antioxidant, and senolytic properties, as demonstrated primarily in preclinical studies. We conducted a structured search and evaluated human translational and clinical studies that utilize fisetin to improve clinical markers associated with age-related low-grade inflammatory diseases. Building on preclinical work and observational studies in humans consuming flavonoid-rich diets or supplements, we evaluated 34 registered clinical trials on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) with a focus on aging/frailty, metabolic diseases, cancer, cardiovascular diseases, neuroimmune/neurodegenerative diseases, and other chronic age-related diseases. We provide the status of the 34 registered trials and a synthesis and discussion of the 4 completed trials with available results that included fisetin, identifying gaps and areas for future investigation. Overall, the completed trials indicate that clinical evidence for fisetin remains limited and heterogeneous. While some studies reported favorable changes in metabolic or inflammatory outcomes, others found no clear or significant clinical benefit. Interpretation is further limited by small sample sizes, multimodal interventions, and uncontrolled or exploratory designs, making it difficult to establish fisetin efficacy in humans. Early findings in animal models and in human cell lines suggest that fisetin has the potential to mitigate age-related diseases by targeting chronic inflammation and oxidative stress driven by increased senescent cell burden, but more clinical data are needed.