1a. Objectives (from AD-416):
LAB NAME: Nutrition, Exercise Physiology, and Sarcopenia 1. Characterize the mechanisms associated with nutritional and contraction-related mediators of anabolic resistance associated with advancing age and/or obesity in animal models and humans. 2. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on physical functioning in older adults with chronic kidney disease or limited mobility. 3. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on cognitive functioning in older adults with chronic kidney disease or limited mobility.
1b. Approach (from AD-416):
LAB NAME: Nutrition, Exercise Physiology, and Sarcopenia Sarcopenia, the age-associated loss in skeletal muscle mass and function, is a contributing factor to the observed declines in physiological capacity and physical functioning with advancing age. The overall theme of this project will be to conduct basic and clinical studies focused on 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 and cognitive performance and/or physical dysfunction in older individuals. Our basic research program will focus on understanding the molecular mechanisms associated with age-related anabolic resistance in skeletal muscle. These basic studies will be uniquely synergized with our clinical/translational studies designed to evaluate the potential efficacy of nutritional and exercise interventions in older adults. Our proposed clinical studies will further seek to understand the role of structured physical activity and nutritional supplementation on changes in physical function and disability in older adults with mobility limitations as a consequence of anabolic resistance and/or sarcopenia. In addition, we will also examine the role of structured physical activity on changes in cognition and the role of physical activity on dementia risk. The 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:
We have made substantial progress on all objectives outlined in our project plan. In the current project year, we have substantially or fully met nearly all of our approved milestones. Work on objectives 1, Characterize the mechanisms associated with nutritional and contraction-related mediators of anabolic resistance associated with advancing age and/or obesity in animal models and humans; 2, Determine the effects of structured, long-term interventions of aerobic walking and resistance physical activity on physical functioning in older adults with chronic kidney disease or limited mobility; and 3, Determine the effects of structured, long-term interventions of aerobic walking and resistance physical activity on cognitive functioning in older adults with chronic kidney disease or limited mobility is all ongoing. Our major focus for Objective 1 has been to optimize our capacity to perform experiments using skeletal muscle cell culture models. We have now optimized our procedures using both immortalized muscle cell culture lines (C2C12 cells) and primary cultures (myoblasts and myotubes) obtained from human skeletal muscle biopsy specimens. These experimental approaches are now being used to examine the effects of specific skeletal muscle microRNA on measures of skeletal muscle protein synthesis and growth capacity. In addition, we are investigating the effects of specific nutrients (carnitine, creatine, and varying chain length fatty acids) on skeletal muscle protein synthesis and growth capacity using these same cell culture systems. For Objectives 2 and 3, the proposed clinical trials are nearing completion, and results from one of these projects is being reported ahead of schedule (see accomplishment 2). In addition, we have expanded our work on metabolomics to the study of the gut microbiome and the role that gut microbiome-derived metabolites play on the age-related loss of skeletal muscle mass and function: sarcopenia.
1. Enhancing independence using group-based community interventions for healthy aging in elders. Results from the Lifestyle Interventions and Independence for Elders (LIFE) study, conducted by ARS-funded researchers in Boston, Massachusetts, demonstrated that a moderate-intensity program of physical activity (PA) dramatically reduced the onset of major mobility disability in older adults. Despite the importance of this finding, a critical unanswered question remains: whether the LIFE study physical activity intervention can be successfully translated to benefit broader populations of at-risk older adults in real-world community settings. ARS-funded researchers at Boston, Massachusetts, recently addressed this key knowledge gap by conducting the ENGAGE Pilot Study (ENhancing independence using Group-based community interventions for healthy AGing in Elders): the first translational study to examine the safety, feasibility and preliminary effectiveness of implementing physical activity into an urban senior center in Greater Boston and target older adults with severe mobility limitations. ENGAGE revealed that physical activity, compared to a healthy aging education program, was safe, easy to follow, and was associated with better preservation of mobility, lower rates of falls and clinically significant improvements in executive cognitive functioning. These initial findings are encouraging and emphasize that larger-scale studies should be performed to translate the benefits of physical activity to broader populations of vulnerable older adults in community-based settings.
2. Nutritional supplementation with physical activity improves muscle composition in mobility-limited older adults: The Vitality, Independence, and Vigor Study 2 (VIVE2). Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The long-term effects of nutritional supplementation in combination with physical activity in older adults, particularly in older adults with limited mobility, remain unclear. ARS-funded researchers in Boston, Massachusetts, examined total-body composition, thigh muscle composition, and muscle strength in older adults with limited mobility and vitamin D insufficiency in response to a 6-month physical activity program. One group of participants consumed a daily nutritional supplement and the other consumed a placebo during the 6-month program. Both groups experienced decreases in total body fat mass and increases in thigh muscle size, but participants receiving the nutritional supplement experienced greater declines in fat accumulation between muscles in the thigh and a greater increase in normal density muscle size than those receiving placebo. These results highlight the synergistic effects of exercise and nutritional supplementation on fat accumulation and skeletal muscle composition in older adults with limited mobility.
Wang, C., Schmid, C.H., Iversen, M.D., Harvey, W.F., Fielding, R.A., Driban, J.B., Price, L., Wong, J.B., Reid, K.F., Rones, R., Mcalindon, T. 2016. Comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: a randomized trial. Annals Of Internal Medicine. doi: 10.7326/M15-2143.
Lustgarten, M., Fielding, R.A. 2016. Metabolites associated with circulating interleukin-6 in older adults. Journal of Gerontology. doi: 10.1093/gerona/glw039.
Gill, T.M., Pahor, M., Guralnik, J.M., McDermott, M.M., King, A.C., Buford, T.W., Strotmeyer, E.S., Nelson, M.E., Sink, K.M., Demons, J.L., Kashaf, S.S., Walkup, M.P., Miller, M.E., Reid, K.F., Fielding, R.A. 2016. Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study). British Medical Journal. doi: 10.1136/bmj.i245.
Sink, K.M., Espeland, M.A., Castro, C.M., Church, T., Cohen, R., Dodson, J.A., Guralnik, J., Hendrie, H.C., Jennings, J., Katula, J., Lopez, O.L., McDermott, M.M., Pahor, M., Reid, K.F., Rushing, J., Verghese, J., Rapp, S., Williamson, J.D. 2015. Effect of a 24-month physical activity intervention vs health education on cognitive outcomes in sedentary older adults: the LIFE randomized trial. Journal of the American Medical Association. 314(8):781-790.