Project Number: 1950-51000-066-02
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2006
End Date: Sep 30, 2011

Objective:
LAB: Nutrition, Exercise Physiology, and Sarcopenia To investigate the influence of nutritional, hormonal and immunologic mediators on the development of skeletal muscle atrophy with advancing age (Sarcopenia). To determine the effects of physical activity/inactivity and protein nutrition on the control of skeletal muscle protein turnover with aging and age-related chronic diseases. To delineate the neuromuscular and musculoskeletal determinants of physical disability and fraility with advancing age and explore the role of targeted exercise and nutritional interventions on attenuating the age-associated progression to fraility and physical disablement.

Approach:
Because sarcopenia is a contributing factor in the development of deficits in function and physical disability, a combination of basic and clinical studies are proposed to examine this syndrome. We will examine cellular alterations associated with sarcopenia which include decreases in muscle fiber size, contractile, and metabolic capacity will further refine our understanding of the proximal determinants of mobility limitations and disability in the elderly. Approaches will include: assessment of whole and regional body composition using DEXA, CT, and MRI; assessment of muscle fiber size, metabolic capacity, and contractile properties using percutaneous needle biopsy; and assessment of whole body function and exercise capacity. In addition, 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, exercise) should accelerate our ability to translate these findings to aging people. Both dietary intervention studies and basic studies are proposed to examine skeletal muscle changes. Approaches will include western blot analysis of key muscle signaling proteins, RT-PCR to measure muscle cytokine gene expression, and several experimental models that manipulate muscle loading condition (eg: synergist muscle ablation, hindlimb unweighting, and electrical stimulation). Finally, the development of novel nutritional and physical activity interventions targeted at specific pathophysiological changes and conditions in older adults with sarcopenia will be examined. Intervention studies are proposed in older men and women to examine the influence of exercise and physical activity on alterations in physical functioning and disability. Approaches will include measures of muscle strength and power, physical performance, and assessment of disability.