Vibegron for ENergy Thinking and Resilience in Aging

Aging is characterized by the gradual loss of physiological integrity, and this process may be accelerated in the presence of obesity, increasing susceptibility to disease, frailty, and death. Although the shared molecular pathways involved have not been fully elucidated, adipose tissue dysfunction is likely a key contributor to multisystem functional decline in aging and obesity. Despite growing evidence that β3 adrenergic receptor (β3AR) mediated activation of brown adipose tissue (BAT) may alter pathophysiological pathways implicated in various aging-related diseases including metabolic, cardiovascular, and neurodegenerative diseases, BAT has been largely ignored in aging research. This study will randomize 40 middle-aged and older adults (45-75 yrs) with obesity to the β3AR agonist Vibegron (75 mg/day) or placebo for 12 weeks to compare their effects on various bioenergetic, cardiometabolic, physical function, and cognitive outcomes. Potential study candidates will be screened by telephone to determine basic interest and eligibility. Individuals who pass this initial screening will then undergo an in-person screening at Atrium Health Wake Forest Baptist. Enrolled participants will be randomized 1:1 to Vibegron or placebo and will be instructed to take the study drug by mouth once daily for 12 weeks. Study outcomes will be assessed at the baseline and follow-up visits and at one safety/compliance visit. Participants will self-report demographic, behavioral, and medical information using questionnaires. They will also complete functional tests to assess muscle strength/power and mobility, DXA and CT scans to assess body composition and body fat distribution, and remote monitoring to assess core body temperature. In addition, participants will have their blood drawn for the assessment of glucose/insulin and lipid indices, for screening and safety purposes, and for storage of plasma/serum samples. Blood samples will also be used to assess mitochondrial bioenergetics in peripheral blood mononuclear cells and thermogenic and adipokine protein expression in adipose tissue-derived small extracellular vesicles. Safety will be assessed based on treatment-related adverse events and measurement of blood chemistries and vitals. To assess medication adherence, participants will be instructed to keep a daily dosing diary and to bring the log, along with empty pill bottles, to the safety/compliance visit for review by the study team.

• Glucose Tolerance Level [Срок оценки: Baseline and Week 12]
• Expanded Short Physical Performance Battery (eSPPB) [Срок оценки: Baseline and Week 12]