Nutrition and Exercise for Sarcopenia

Our preliminary studies indicate that, in older adults, muscle protein anabolism is normally stimulated by amino acids alone, but impaired when nutritional stimuli contain carbohydrate due to a relative insulin resistance of muscle protein synthesis. We have also found that amino acids are the most efficient nutrients for the acute stimulation of muscle protein anabolism and our pilot data suggest that they can also increase muscle mass in healthy older adults. Inactivity is another likely contributor to sarcopenia. Exercise increases not only muscle protein synthesis,mass and strength, but also energy expenditure. Hence, exercise may improve the response of muscle to nutritional interventions in older subjects via increased energy requirements and food consumption, thereby allowing for achievement of true supplementation. We will test the following specific hypotheses in older, community indwelling, sedentary subjects: Using a factorial design we will address in older, community-indwelling, sedentary subjects the following hypotheses: 1. Nutritional supplementation with amino acids will improve muscle mass, strength, function, quality, and protein synthesis. 2. Progressive exercise training for 24 weeks will improve muscle mass strength,function, quality, perfusion, and protein metabolism. 3. Combined treatment with nutritional supplementation and progressive exercise training for 24 weeks will improve muscle mass, strength, function, quality, perfusion, and protein metabolism more than either intervention alone. Our goal is to establish if specific interventions that can acutely increase muscle protein synthesis can also effectively translate into increased muscle mass and/or performance in older sedentary people, thus preventing frailty and promoting physical independence. To this end we will use stable isotope methodologies to measure muscle protein metabolism and contrast enhanced ultrasound to measure muscle perfusion, in order to determine if the treatments' acute effects can predict their chronic impact on muscle mass and function. We will also determine if chronic treatment leads to metabolic and/or vascular adaptations that may explain the measured changes in muscle mass and function.