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:
Have examined the role that specific fat molecules have on skeletal muscle growth capacity in both animal models and human subjects. We have found that with advancing age there is an increased accumulation of specific types of fats (ceramides) and these type of fat have effects on muscle growth capacity. We are also in the process of completing complementary studies on both muscle growth capacity in older humans, and studies examining differences in skeletal muscle growth capacity in young and older healthy adults in the current project year. Interestingly, in humans, we have observed that the concentration of these ceramide molecules in muscle samples is closely associated with the total amount of muscle mass. These data suggest that ceramides may play a regulatory role in skeletal muscle growth processes and may be linked to the development of sarcopenia. We are presently evaluating interventions to manipulate ceramide levels in skeletal muscle and examine the effects on skeletal muscle growth capacity. Work on determining the efficacy of selected nutritional and lifestyle behaviors on age-related changes in skeletal muscle physiology and physical functioning is in progress. We recently completed our study examining the influence of a 40 g per day supplement of whey protein on changes in muscle mass, strength, physical performance in older men and women with mobility limitations. A total of 80 older men and women (70-85 years) were assigned to receive either 40 g of whey protein per day or an equivalent amount of calories without protein together with a resistance exercise training program (strength training) for 6 months. We found that both groups had significant and meaningful improvements in their muscle mass and strength in response to this intervention but there was no added benefit of the whey protein supplement on this response. Interestingly, however, the subjects who received the whey protein supplement plus exercise had a significant lowering of their systolic blood pressure (-8 mmHg reduction) compared to the placebo plus exercise group (-2 mmHg reduction). These data suggest that whey protein supplementation in this population of older adults does not offer added benefit in conjunction with resistance training exercise in terms of changes in muscle strength or mass but may have clinically important benefits on cardiovascular disease risk reduction. The LIFE (Lifestyle Interventions and Independence for Elders) study has reached a significant milestone with the completion of recruitment of 1635 older men and women nationally (202 at Tufts HNRCA field center). All recruitment goals and targets for LIFE were met nationally and at the local Tufts HNRCA field center. This study will examine whether a structured program of physical activity will prevent the development of late life disability and improve cognitive function in at-risk older adults. When completed, the LIFE study will be the largest clinical trial of a physical activity intervention ever conducted in older adults.
1. Muscle power failure in mobility-limited older adults. The age associated loss of lower extremity skeletal muscle power has emerged as a critical determinant of functional independence and mobility among older adults. However, limited knowledge exists on the major underlying physiological factors that determine muscle power generation with advancing age in healthy or mobility-limited older populations. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, Massachusetts, found that muscle power, strength, muscle mass, quality and neuromuscular function were significantly lower among mobility-limited elders compared to healthy adults without mobility-limitations. Conversely, muscle biopsy samples revealed that the contractile properties of single muscle cells were preserved in mobility-limited elders relative to healthy subjects. The dissociation between age-related changes at the whole muscle and cellular level suggest that, even among older adults with overt mobility problems, contractile properties of surviving muscle cells are preserved in an attempt to maintain overall muscle power and function.