2011 Annual Report 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 a subordinate project at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-068-01S (Nutrition, Physical Activity, and Sarcopenia in the Elderly). 4.Accomplishments 1. Regulators of lipid (fat) synthesis are increased in aging skeletal muscle. With advancing age, several reports have noted an increase in the content of triglyceride (fat) in skeletal muscle. This increase in muscle triglyceride has been associated with the development of insulin resistance, elevated risk of Type II diabetes, and may be related to skeletal muscle growth capacity. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, found that not only is skeletal muscle triglyceride increased with advancing age but several of the major regulators (genes and proteins) of triglyceride synthesis are also increased. These results suggest that age-associated triglyceride accumulation in skeletal muscle is an active process that is driven by increased biosynthetic capacity for lipid synthesis. These results may lead to the development of specific targets to alter insulin resistance and enhance muscle growth capacity that are directed at regulators of lipid synthesis in muscle. 2. Increases in bioactive lipids alter anabolic signaling in aging humans. It is well established that an increased accumulation of lipids and their various metabolites within skeletal muscle are directly related to reductions in insulin-stimulated glucose uptake (insulin resistance). However, far less is known about their role in the control of skeletal muscle protein turnover and anabolic signaling. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, found that following a single strength training exercise session, young men had a significant increase in several growth-activating proteins in their muscle while these proteins were unchanged in the muscle of older men following a similar exercise session. They also observed increases in several lipids in muscle, including ceramides, diacylglycerol, and acylcarnitines, from the older men but not the younger men. These results suggest that the accumulation of specific lipids (ceramides, diacylglycerols, and acylcarnitines) in muscle with advancing age may play a role in the development of sarcopenia. Review Publications Morie, M., Reid, K., Miciek, R., Lajevardi, N., Choong, K., Krasnoff, J.B., Storer, T.W., Fielding, R., Bhasin, S., Lebrasseur, N.K. 2010. Habitual physical activity levels are associated with performance in measures of physical function and mobility in older men. Journal of the American Geriatrics Society. 59(9):1727-1733. Pasiakos, S.M., Mcclung, H.L., Mcclung, J.P., Urso, M.L., Cloutier, G.J., Fielding, R.A. 2010. Molecular responses to moderate endurance exercise in skeletal muscle. International Journal of Sport Nutrition and Exercise Metabolism. 20(4):282-290. Morie, M., Reid, K., Miciek, R., Lajevardi, N., Choong, K., Krasnoff, J., Storer, J., Fielding, R.A., Bhasin, S., Lebrassuer, N. 2010. Habitual physical activity levels are associated with performance in measures of physical function and mobility in older men. Journal of the American Geriatrics Society. 58(9):1727-1733. Sparrow, D., Gottlieb, D., Demolles, D., Fielding, R. 2011. Increases in muscle strength and balance using a resistance training program administered via a telecommunications system in older adults. Journal of Gerontology Medical Science. DOI: 10.1093/gerona/girl38. Fielding, R.A., Liu, C.K. 2011. Exercise as an intervention for frailty. Clinics in Geriatric Medicine. 27(1):101-110. Clark, D.J., Patten, C., Redi, K.F., Carabello, R.J., Fielding, R.A. 2011. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults. Journal of the American Geriatrics Society. 58(1):1918-1924. Chale-Rush, A., Guralnik, J.M., Walkup, M.P., Miller, M.E., Rejeski, W., Katula, J.A., King, A.C., Glynn, N.W., Manini, T.M., Blair, S.N., Fielding, R.A. 2010. Relationship between physical functioning and physical activity in the lifestyle interventions and independence for elders pilot. Journal of the American Geriatrics Society. 58(10):1918-1924. Chumlea, W.C., Cesari, M., Evans, W.J., Ferrucci, L., Fielding, R.A., Pahor, M., Studendski, S., Vellas, B. 2011. Sarcopenia: designing phase IIb trials: international working group on sarcopenia. Journal of Nutrition Health and Aging. 15(6):450-455. Clark, D.J., Patten, C., Reid, K.F., Carabello, R.J., Fielding, R.A. 2010. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults. Journals of Gerontology. 65(5):495-502. Fielding, R., Rejeski, W., Blair, S., Church, T., Espeland, M., Gill, T., Guralnik, J., Hsu, F., Katula, J., King, A., Kritchevsky, S., Mcdermott, M., Miller, M., Nayfield, S., Newman, A., Williamson, J., Bonds, D., Romashkan, S., Hadley, E., Pahor, M. 2011. The lifestyle interventions and independence for elders study: design and methods. Journal of Gerontology Biological Science. DOI: 10.1093/gerona/girl123. Lustgarten, M., Fielding, R. 2011. Assessment of analytical methods used to measure changes in body composition in the elderly and recommendations for their use in phase II clinical trials. Journal of Nutrition Health and Aging. 15(5):368-375. PMID:21528163. Pasiakos, S., Mcclung, H., Mcclung, J., Margolis, L., Andersen, N., Cloutier, G., Pikosky, M., Rood, J., Fielding, R., Young, A. 2011. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. American Society for Clinical Nutrition. DOI: 10.3945/ajcn.111.017061. PMID:21775557.