Lifestyle intervention to improve muscle function in older adults

/ABSTRACT In the United States, nearly one third of adults over 60 years of age have sarcopenic obesity which encompasses the combined effect of muscle impairment and obesity. Inducing loss of fat mass while slowing or preventing loss of skeletal muscle mass and quality are critical for preserving the musculoskeletal, cardiometabolic, and cognitive benefits of weight loss in older adults with obesity. As people age, muscle mass and quality decrease while fat mass progressively increases, and these body composition changes are associated with increased incidence of insulin resistance. Calorie restriction and exercise reduce body mass and improve physical performance but lean mass accounts for 22% to 33% of weight loss. Moreover, behavioral adaptations to calorie restriction make adherence a challenge. Energy deficits can be achieved without conscious practice. Since people tend to eat a consistent weight of food, eating a diet low in energy density reduces energy intake. Diets low in energy density reduce body weight and fat mass and moderate the loss of lean mass. Reduced energy intake combined with exercise increases fat loss and improves physical performance more than exercise alone. To date, no adequately powered randomized controlled feeding trial > 14 days has determined the effect of a diet low in energy density on metabolic outcomes. The proposed study will test the hypothesis that a diet low in energy density + exercise (1.0 kcal/g, LD+E) reduces fat mass (Aim 1), improves muscle function (Aim 2) and increases energy deficit (Aim 3). We will conduct a 12-week trial in 80 older adults (> 50 years) with obesity and insulin resistance. Participants will be randomized to LD+E or to the diet typically consumed by older adults + exercise (2.0 kcal/g, TD+E). Baseline energy requirements will be determined using an equation derived from doubly labeled water assessments. All meals for 12 weeks will be prepared in our metabolic kitchen. The macronutrient composition of the diet will be 40-45% carbohydrate; 20- 25% protein; and 35-40% fat. Participants will engage in a combination of supervised aerobic and resistance training for a total of 150 minutes per week, for 12 weeks. Aim 1 will test the hypothesis that LD+E reduces fat mass (dual x-ray absorptiometry) and moderates the loss of lean mass (creatine [methyl-d3] dilution) compared to TD+E. Aim 2 will test the hypothesis that LD+E improves muscle function (short physical performance battery, hand grip strength, six-minute walk test, and VO2 max test). Aim 3 will test the hypothesis that LD+E produces an energy deficit (changes in fat and fat-free mass). Using structural equation models, we will test the effect of circulating concentrations of glucagon-like peptide 1, gastric inhibitory peptide, cortisol, and leptin on energy balance and muscle function. Impairment of skeletal muscle function poses a serious health challenge especially in the context of the demographic trend towards an aging population. The hypothesized outcomes are of far-reaching consequence with the advent of incretin-based pharmacotherapy to treat obesity that causes rapid and significant loss of lean mass comparable to a decade or more of aging. Project Number: 1R01AG092725-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Candida Rebello | Institution: LSU PENNINGTON BIOMEDICAL RESEARCH CTR, BATON ROUGE, LA | Award Amount: $749,481 | Activity Code: R01 | Study Section: Lifestyle Change and Behavioral Health Study Section[LCBH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11298570