Fisetin to Reduce Senescence and Mobility Impairment in PAD

The investigators propose a pilot randomized trial to gather preliminary data to test the hypothesis that Fisetin will reduce abundance of senescent cells in blood, skeletal muscle, and both subcutaneous and inter muscular adipose tissue and improve 6-minute walk distance in 34 people with peripheral artery disease (PAD). the investigators will determine whether greater declines in abundance of cells with senescent markers are associated with greater improvement in 6-minute walk distance in people with peripheral artery disease. In exploratory analyses, the investigators will assess whether Fisetin reduces interleukin-6 (IL-6) and novel senescent markers in adipose tissue, muscle, and/or blood.

Fisetin is a flavanol, present in strawberries, apples, and persimmons, that destroys senescent cells (i.e. a senolytic therapy). Of three senolytic therapies being tested in clinical trials, Fisetin has the best safety profile. Hence, the investigators propose a pilot randomized trial to gather preliminary data to test the hypothesis that Fisetin will reduce abundance of senescent cells in blood, skeletal muscle, and both subcutaneous and inter muscular adipose tissue and improve 6-minute walk distance in 34 people with PAD. The investigators will determine whether greater declines in abundance of cells with senescent markers are associated with greater improvement in 6-minute walk distance in people with PAD. In exploratory analyses, the investigators will assess whether Fisetin reduces IL-6 and novel senescent markers in adipose tissue, muscle, and/or blood. To achieve the trial's specific aims, investigators will randomize 34 participants age 50 and older with PAD to one of two groups: Fisetin vs placebo. Participants will be followed for four months.