Our general hypothesis is that nutritional factors and inactivity play significant roles in the development of sarcopenia. Thus, age-specific prolonged interventions including nutritional manipulations and/or exercise may help to reduce, stabilize, or even reverse the loss of muscle mass and strength with age. However, previous studies attempting to improve muscle mass in older subjects using nutritional supplementation had little success, due to a trend for elders to compensate for the energy delivered by nutritional supplements with reduced food intake. Therefore, effective nutritional supplements for the elderly should be more anabolic than the same amount of ordinary food, to limit the caloric content and maximize the anabolic efficiency (anabolic effect/energy delivered). Our preliminary data indicate that essential amino acids are the most efficient nutrients for the acute stimulation of muscle protein anabolism, and that long term utilization may also improve muscle mass in older subjects. Additionally, inactivity is another likely contributor to sarcopenia. Exercise increases not only muscle mass and strength, but also energy expenditure. Hence, exercise may improve the response of muscle to nutritional supplementation in older subjects via increased energy requirements and food consumption, thereby allowing for the achievement of true supplementation. Although resistance exercise is the most anabolic form of physical activity, compliance in the outpatient setting may be disappointing. Aerobic exercise is more appealing and easier to implement in the older population. Our preliminary data indicate that aerobic exercise acutely increases muscle protein synthesis, normalizes muscle perfusion, and reduces the age-related insulin resistance of muscle proteins. Thus, aerobic exercise may improve muscle protein metabolism, strength, function and even mass in older people, particularly when combined with nutritional interventions. We will test the following specific hypotheses in older sedentary subjects: 1. A highly efficient nutritional supplement will increase, with prolonged treatment, muscle mass and strength by stimulating net muscle protein synthesis. 2. Progressive aerobic training will increase muscle strength and function by stimulating muscle protein turnover and improving muscle perfusion and muscle quality. 3. The highly efficient nutritional supplementation combined with progressive aerobic training will increase muscle mass, strength, and function more than either intervention alone by additively stimulating net muscle protein synthesis, and improving muscle perfusion and muscle quality. Our goal is to establish if specific interventions that can acutely increase muscle protein synthesis can also effectively translate into increased muscle mass and performance in older sedentary people. PROJECT NARRATIVE Our general goal is to find simple and safe interventions to prevent and treat the loss of muscle mass, strength, and function in older persons. Muscle weakness with aging leads to frailty, disability and loss of independence, increasing the risk of institutionalization and death, and greatly increasing healthcare costs. Based on our preliminary data, we propose that prolonged nutritional supplementation with highly effective, age-specific supplements and/or endurance training will enhance muscle mass, strength and function in older persons by increasing muscle growth and quality.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-EMNR-G (02))
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Joseph, Lyndon
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University of Texas Medical Br Galveston
Internal Medicine/Medicine
Schools of Medicine
United States
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Markofski, Melissa M; Jennings, Kristofer; Timmerman, Kyle L et al. (2018) Effect of Aerobic Exercise Training and Essential Amino Acid Supplementation for 24 Weeks on Physical Function, Body Composition and Muscle Metabolism in Healthy, Independent Older Adults: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci :
Deer, Rachel R; Volpi, Elena (2015) Protein intake and muscle function in older adults. Curr Opin Clin Nutr Metab Care 18:248-53
Markofski, Melissa M; Dickinson, Jared M; Drummond, Micah J et al. (2015) Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women. Exp Gerontol 65:1-7
Dickinson, Jared M; Gundermann, David M; Walker, Dillon K et al. (2014) Leucine-enriched amino acid ingestion after resistance exercise prolongs myofibrillar protein synthesis and amino acid transporter expression in older men. J Nutr 144:1694-702
Dickinson, Jared M; Rasmussen, Blake B (2013) Amino acid transporters in the regulation of human skeletal muscle protein metabolism. Curr Opin Clin Nutr Metab Care 16:638-44
Dickinson, Jared M; Volpi, Elena; Rasmussen, Blake B (2013) Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle. Exerc Sport Sci Rev 41:216-23
Markofski, Melissa M; Volpi, Elena (2011) Protein metabolism in women and men: similarities and disparities. Curr Opin Clin Nutr Metab Care 14:93-7
Johnson, Mary Ann; Dwyer, Johanna T; Jensen, Gordon L et al. (2011) Challenges and new opportunities for clinical nutrition interventions in the aged. J Nutr 141:535-41