There is growing interest among the general population in preventive health interventions that can help mitigate age-related decline, reduce the risk of chronic diseases, and promote healthy aging. The use of nutritional supplements has been increasing and is especially high in older adults and healthier individuals. In response to this demand, a growing number of nutritional supplements are being advertised for their "anti-aging" properties, claiming to target molecular and cellular "hallmarks of aging", such as chronic inflammation, oxidative stress, and cellular senescence. However, the overwhelming majority of these claims stem from preclinical studies in animal models (e.g., C. elegans, mice), and there is extremely limited evidence for beneficial effects, effective doses, or safety profiles of these supplements in humans. Moreover, the lack of strict regulations in the nutritional supplement industry leads to wide differences in the quality and in the actual content of active substances between supplements, which could impact both their efficacy and safety.

The investigators will conduct a clinical trial in healthy volunteers, who will receive supplementation with fisetin (100 mg) or placebo daily for 7 weeks. Participants will be examined at regular intervals during the study period. The investigators will then investigate whether fisetin supplementation is safe and evaluate its effect on measures of chronic inflammation, cellular senescence, aging, and general health.

The goal of this study is to assess the anti-inflammatory effects, overall health benefits, and the safety of a daily low dose (100 mg) of fisetin in relatively healthy middle-aged and older adults.

The study is a 2-arm triple-blind randomized placebo-controlled trial, in which middle-aged and older adults (n=120) will receive either:

• One capsule (100 mg) fisetin daily for 7 weeks (intervention group), or
• One capsule placebo daily for 7 weeks (control group).

Inclusion Criteria:

• Middle-aged or older adult (≥50 years),
• Able to cooperate cognitively,
• Able to read and understand Danish,

Exclusion Criteria:

• Inability or unwillingness to take oral supplements,
• Chronic or recent (within 30 days) use of other anti-aging supplements,
• Chronic or recent (within 30 days) treatment with medications having anti-aging effects (e.g., metformin, rapamycin, semaglutide),
• Chronic or recent (within 30 days) treatment with anti-inflammatory medications,
• Chronic or recent (within 30 days) treatment with the medications that can interact negatively with fisetin,
• Recent (within 14 days) vaccination,
• Treatment with another investigational drug or other intervention within 1 year,
• Active cancer or current cancer treatment,
• Unstable or uncontrolled major disorders, e.g., cardiovascular, renal, endocrine, immunological, hepatic disorder, or cancer, requiring regular monitoring at the hospital
• Planned medical and surgical procedures during the study period,
• Known hypersensitivity or allergy to fisetin or excipients in the placebo capsules,
• Presence of any condition that the investigator believes would put the participant at risk or would preclude the participant from successfully completing all aspects of the study