Ongoing Lung Decline With Age Intensified Response

This Phase II, randomized, double-blind, placebo-controlled pilot study will evaluate the effects of fisetin, a senolytic flavonoid compound, on lung function and biomarkers of cellular senescence in older adults aged 60 years and older. Participants will include individuals with a history of at least 10 pack-years of smoking as well as age-matched never-smokers. Forty participants will be randomized to receive either fisetin or placebo using a short-course "hit-and-run" dosing strategy (approximately 20 mg/kg/day orally for 2 consecutive days on Days 1-2 and Days 8-9).

Inclusion Criteria: * Adults aged 60 years and older who are physically capable of participating in study procedures; * Willing to be randomized to fisetin or placebo; weight stable within the previous 2 months (\110 mmHg. * Known allergy or hypersensitivity to fisetin or any component of the study product. * Active malignancy, except non-melanoma skin cancer. * Clinically significant hepatic, renal, cardiovascular, endocrine, immunologic, metabolic, or other uncontrolled medical conditions that, in the opinion of the investigator, would interfere with study participation or interpretation of results. * Clinically significant laboratory abnormalities, including severe anemia, leukopenia, thrombocytopenia, uncontrolled diabetes, advanced kidney disease, significant liver dysfunction, or evidence of systemic inflammation. * Human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C infection, or invasive fungal infection. * History of diverticulitis or diverticulosis with gastrointestinal bleeding. * Current use of systemic corticosteroids. * Current use of warfarin. * Current use of medications with significant interaction potential with fisetin, including selected CYP450 or transporter substrates, inhibitors, or inducers, unless such medications can be safely withheld according to protocol requirements. * Recent medication, supplement, or lifestyle changes that may affect study outcomes, in the opinion of the investigator. * Inability to perform required study procedures, including pulmonary function testing, exercise testing, or other protocol assessments. * Unwillingness or inability to provide informed consent. * Pregnancy or breastfeeding. * Any other condition that, in the opinion of the investigator, would make participation unsafe or compromise study integrity.