Skeletal Muscle Protein Metabolism and Molecular Responses to Endurance Exercise and Nutritional Interventions

It has been suggested that the gradual loss of muscle mass observed with healthy aging is the result of a resistance of aged muscle tissue to normally potent anabolic stimuli. Recent evidence indicates an age-related anabolic resistance in skeletal muscle tissue to exogenous amino acids and to a wide range of resistance exercise intensities. In addition, aging is associated with adaptations within the vascular system that may adversely affect blood flow, thereby potentially impacting amino acid delivery, exchange and utilization. Endurance-type exercises have been shown to elicit significant increases in muscle blood flow and stimulate muscle protein synthesis; however, it is not known whether age-related anabolic resistance occurs in response to endurance exercise. These studies were designed and implemented to determine whether endurance exercise and amino acid supplementation independently and synergistically contribute to the stimulation of skeletal muscle protein synthesis. Stable isotopic techniques (i.e. arteriovenous balance measurements and tracer incorporation), macro- (indocyanine green dye dilution and Doppler) and microvascular (contrast-enhanced ultrasound and microdialysis) techniques, immunoblotting, and hormone assays were used to examine skeletal muscle metabolism, leg blood flow and skeletal muscle perfusion, and intracellular signaling events associated with translational control of muscle protein accretion. The principal findings are that acute endurance exercise increases amino acid exchange stimulating muscle protein synthesis without an age-related resistance to the anabolic effects of exogenous amino acids during exercise. This is contradictory to the situation following endurance-type exercise; when older adults exhibit anabolic resistance to exogenous amino acids. It is important to note that this age-related anabolic resistance did not manifest into an overall decrement in net protein balance. The molecular events underlying these changes are marked by increases in the activation of proteins involved in muscle hypertrophy signaling, and decreases in muscle atrophy signaling. Lastly, daily leucine supplementation enhances the anabolic stimulus of a mixed nutrient meal in older adults. Taken together, these results suggest that endurance exercise and amino acids, specifically leucine, are effective interventional strategies that may be used to stimulate muscle protein anabolism in older adults to ameliorate or prevent muscle loss.