Fisetin to Improve Vascular Function in Older Adults

Inclusion Criteria:

• Age 65 years or older

• Women must be postmenopausal

• Body mass index (BMI) <40 kg/m2

• Willing to accept random assignment

• Weight stable in the prior 2 months (<2 kg weight change) and willing to remainweight stable throughout the study

• Ability to understand study procedures and to comply with them for the entire lengthof the study

• No blood donation within 8 weeks prior to baseline testing; willingness to abstainfrom blood donation during the study and for 8 weeks after study completion

• Absence of established, serious, unstable, chronic clinical disease (e.g., unstableCVD) as determined by study physician of record based on subject medical history,physical examination, resting ECG and standard clinical blood chemistries

Exclusion Criteria:

• Inability to refrain from alcohol for 24 hours prior to outcome assessment

• Individuals taking fisetin, quercetin, luteolin, Dasatinib, piperlongumine orNavitoclax (supplements or drugs with established senolytic effects) within 6 monthsprior to baseline testing; should new research reveal other dietary supplements ordrugs with potential senolytic effects, their use will be evaluated, and their usemay lead to exclusion of the subject by the PI

• New use of regular cardiovascular-acting medication which, in the opinion of the PI,affects the outcomes of the study within 3 months prior to starting baseline testingas reported during medication review during screening (these individuals could beenrolled after 3 months of regular use)

• Chronic use of a dietary supplement which, in the opinion of the PI, affects theoutcomes of the study, within 1 month prior to starting baseline testing as reportedduring medication review during screening (these individuals could be enrolled after 1 month of regular use)

• Active malignancy (including myeloma) or malignancy that was active within 5 yearsprior to baseline testing

• Inability or unwillingness of individual to give written informed consent

• Current or past participation within 3 months in another clinical trial that, in theopinion of the PI, would affect the outcomes of the study

• Known hypersensitivity or allergy to fisetin

• Blood donation within 2 months prior to baseline testing

• Resting blood pressure >160 mmHg systolic or >110 mmHg diastolic

• Regular vigorous aerobic/endurance exercise