Mechanisms of Anabolic Resistance in Older Humans

Inflamed adipose tissue may contribute to blunted exercise response in skeletal muscle of older adults. The objective of this project is to evaluate a hypothesis that inflamed adipose secretes factors that activate inflammatory cascades in skeletal muscle, which may interfere with exercise-responsive molecular pathways and contribute to dysfunctional muscle phenotypes with aging. This project determine how adipose tissue influences skeletal muscle function and anabolic response to exercise in older adults. Young and older adults will complete studies to assess molecular response to acute exercise from protein synthesis rates, mRNA of exercise-responsive genes, and activation of signaling proteins in skeletal muscle. Adipose tissue will be assessed using a combination of non-invasive imaging and biopsy-based molecular phenotyping. The project will determine if acute exercise response is attenuated in older adults with inflamed adipose tissue phenotype.

Exclusion criteria

• Diabetes or fasting plasma glucose 126 mg/dL
• Body mass index (BMI) 30 kg/m2
• Anemia (female subjects hemoglobin of <11 g/dl and male subjects hemoglobin <12 g/dl)
• Active coronary artery disease or history of unstable macrovascular disease (unstable angina, myocardial infarction, stroke, and revascularization of coronary, peripheral or carotid artery within 3 months of recruitment)
• Renal failure (serum creatinine > 1.5mg/dl)
• Chronic active liver disease (AST>144IU/L or ALT>165IU/L)
• Oral warfarin group medications or history of blood clotting disorders.
• Smoking
• Pregnancy or breastfeeding
• Alcohol consumption greater than 2 glasses/day or other substance abuse
• Untreated or uncontrolled hypothyroidism
• Debilitating chronic disease (at the discretion of the investigators)