Obesity Clinical Trial
Official title:
Single Nuclei RNA-sequencing to Map Adipose Cellular Populations and Senescent Cells in Older Subjects
All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq and metabolic/physiological assessments (insulin sensitivity, glucose tolerance, and β-cell function). Older obese participants will be randomized into three arms: lifestyle intervention (n=24), senolytics (n=24), or placebo (n=24).
All participants after consent and enrollment will undergo adipose tissue single nuclei RNA sequencing and metabolic phenotyping. Subjects will undergo glucose tolerance testing to document glucose tolerance status. Each subject will be provided an accelerometer to be worn on their dominant wrist for 7 days for assessment of habitual activity. A dietitian will teach them to utilize the SmartIntake3 smartphone food picture application (app) for a 7-day food record. The app will be used to record amount of each meal consumed in order to determine daily food and beverage and supplement intake and quantity for dietary composition analysis. DEXA analysis will be performed to measure lean and fat body mass. Subjects will undergo evaluation of physical function/performance, including the Short Physical Performance Battery (SPPB) and VO2 peak testing for assessment of aerobic capacity. The SPPB will be done in older adults only. The NIH Patient-Reported Outcomes Measurement System (PROMIS) will be used to measure participants' self-report of symptoms, function, and health-related quality of life in the domains of physical, mental and social health. All subjects will undergo a two-step euglycemic insulin clamp and indirect calorimetry. Only older obese participants will continue to the randomization to likestyle intervention, senolytic agents or placebo. ;
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