1a. Objectives (from AD-416):
1. Investigate the nutritional and activity-related mediators of skeletal muscle atrophy associated with advancing age in animal and human studies. 2. Evaluate the chronic effects of dietary proteins/amino acids and physical activity/inactivity on changes in skeletal muscle structure and function and physical functioning in at-risk older individuals.
1b. Approach (from AD-416):
Sarcopenia, the age-associated loss in skeletal muscle mass, is a contributing factor to the observed declines in physiological capacity and functional performance with advancing age. The economic impact of sarcopenia has been estimated at $18.5 billion, annually. The overall theme of this project will be to use a platform-based approach in the identification, evaluation, and understanding of nutritional and physical activity interventions that possess anabolic properties in skeletal muscle and have the potential to prevent or reverse impaired motor performance and/or physical dysfunction in older individuals. Using our well characterized rodent model of human sarcopenia, we propose to examine the mechanisms and efficacy of nutrient modulation on overload-induced skeletal muscle hypertrophy. We then propose to perform parallel clinical studies to examine the influence of physical activity/exercise and nutrition on the control of muscle protein turnover in older adults with defined low muscle mass and functional limitations. We will also evaluate the chronic effects of dietary protein/amino acids and physical activity/inactivity on changes in skeletal muscle structure and function and physical functioning in at risk older adults. Finally, we will examine the effects of a multi-modal physical activity program on changes in muscle mass, strength, physical functioning, and disability in older individuals with clinically demonstrated functional limitations. The unique pairing of clinical studies examining the influence of protein nutrition and physical activity on sarcopenia with basic approaches that identify the molecular landscape and potential targets in skeletal muscle for preventive interventions (nutritional, physical activity) may accelerate our ability to translate these findings to aging people.
3. Progress Report:
This progress report includes the work of one subordinate project at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress report, see 1950-51000-068-01S (Nutrition, physical activity, and sarcopenia in the elderly).
1. NUTRITION, EXERCISE PHYSIOLOGY AND SARCOPENIA LAB: Skeletal Muscle microRNA are altered by age and exercise. Skeletal muscle growth capacity in response to exercise and nutrition is reduced with advancing age. ARS funded researchers at JMUSDA-HNRCA at Tufts University in Boston, Massachusetts measured growth promoting (anabolic) signals and signals that breakdown (catabolic) muscle following strength training exercise in skeletal muscle from healthy young and older men. The older men had reduced growth promoting signals and higher levels of signals that caused muscle breakdown than the younger men after exercise. We also measured a specific type of genetic material called microRNAs which are small segments of RNA. These microRNA are important for the control cellular growth. We found that several types of microRNAs were altered by exercise in young men but did not change in the older men. These data suggest that microRNAs play an important role in the adaptations of skeletal muscle to exercise and that this response is altered with aging.
2. NUTRITION, EXERCISE PHYSIOLOGY AND SARCOPENIA LAB: Serum metabolites are associated with lean mass and muscle size in older functionally limited men and women. Simple blood tests to determine muscle mass in humans currently do not exist. ARS funded researchers at JMUSDA-HNRCA at Tufts University in Boston, Massachusetts measured a panel of over 300 separate compounds in blood samples taken from older men and women who had some difficulty with their mobility. We found that a number of compounds that are by-products of amino acid metabolism (breakdown) were associated with whole body lean mass and muscle size. These data suggest that it may be possible to develop simple blood tests to quantify the total body skeletal muscle mass. Specifically specific metabolites of amino acid metabolism could be measured in the blood to estimate skeletal muscle mass in free living people.Cesari, M., Fielding, R., Pahor, M., Goodpaster, B., Hellerstein, M., Abellan Van Kan, G., Anker, S.D., Rutkove, S., Vrijbloed, J., Isaac, M., Rolland, Y., M'Rini, C., Aubertin-Leheudre, M., Cedarbaum, J.M., Zamboni, G., Sieber, C., Laurent, D., Evans, W.J., Roubenoff, R., Morley, J.E., Vellas, B. 2012. Biomarkers of sarcopenia in clincal trials recommendations from the international working group on sarcopenia. Journal of Cachexia, Sarcopenia and Muscle. 3(3):181-190.