Ongoing Lung Decline With Age Intensified Response (OLD AIR)

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 (<5-pound change);
• No blood donation within 2 months before screening; absence of unstable chronic disease;
• Willing to maintain baseline activity level throughout the study;
• Body mass index <30 kg/m²;
• Either a history of at least 10 pack-years of cigarette smoking or never-smoking status.

Exclusion Criteria:

• Electrocardiogram (ECG) abnormalities, including prolonged QTc.
• Use of fisetin, other flavonoid supplements, or known senolytic compounds within 6 months prior to screening.
• Resting systolic blood pressure >160 mmHg or diastolic blood pressure >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.