Project Number: 8050-51000-104-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: May 16, 2019
End Date: May 30, 2024
Objective 1: Characterize the mechanisms associated with nutritional and exercise related mediators of anabolic resistance associated with sarcopenia, advancing age, and/or reduced mobility in cell/animal models and humans. Sub-objective 1A: Characterize the role of plasticity-related micro-RNA (PR-miRNA) on the anabolic response to specific amino acids, growth factors, and mechanical stretch in skeletal muscle and to further understand the interaction of adipocyte derived micro-RNA on skeletal muscle anabolic capacity. Sub-objective 1B: Characterize in an exploratory manner the association between gut microbiome composition and function with skeletal muscle composition and performance. Objective 2: Determine the mechanisms by which selected nutrients and/or varying modes of exercise/physical activity influence skeletal muscle performance, cognitive performance, physical functioning, and quality of life in older adults. Sub-objective 2A: Characterize the effects of exercise training on skeletal muscle alone or in combination with daily supplementation of '-3 fatty acids in older adults with mobility limitations and chronic low-grade inflammation. Sub-objective 2B: Characterize the safety, scalability and relative suitability of a low-cost physical activity interventions in older adults with motoric cognitive risk syndrome in a community setting.
Sarcopenia, the age-associated loss in skeletal muscle mass and function, is a contributing factor to the observed declines in physiological capacity, reduced functional performance, and increased disability and mortality observed with advancing age. The underlying causes of sarcopenia are multi-factorial but include poor nutritional status, reduced levels of physical activity, inflammation, chronic disease burden and other co-morbidities. This project will continue to use a translational science approach to examine the underlying mechanisms by which nutrition and exercise alter skeletal muscle function, and to identify and evaluate the impact of nutritional and exercise interventions on skeletal muscle performance capacity and their potential to prevent or reverse impaired motor/cognitive performance and/or physical dysfunction in older adults. Specifically, we will continue to interrogate skeletal muscle-derived microRNA and microRNA expressed from adipocytes to understand their role in age-related changes in skeletal muscle gene expression and resultant impact on muscle anabolic capacity. In addition, we will investigate the role of age-related alterations in the gut microbiome on skeletal muscle composition and function. We will evaluate the interactive effects of exercise and omega-3 fatty acids on skeletal muscle composition and function in older adults at risk for mobility disability. Finally, we will evaluate the safety and scalability of a community-based exercise intervention in older adults with cognitive and physical limitations. The pairing of basic approaches that identify the molecular landscape and skeletal muscle targets with clinical studies of nutrition and physical activity on sarcopenia will accelerate our ability to translate these findings to aging people.