AMINO ACID SUPPLEMENTATION AND MUSCLE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Muscle wasting and weakness are common due prolonged inactivity and bedrest. Unfortunately, bedrest is a common occurrence post surgery, serious injury, or chronic illness. The loss of lean body mass (LBM) with inactivity is associated with longer recovery time and a great decrease in overall health status. Due to the greater prevalence of surgeries and serious illnesses in the aging population, the elderly are at an increased risk for morbidity and mortality. Our previous investigations in younger individuals demonstrated that minimal resistance exercise and nutritional supplementation with essential amino acids can maintain LBM and preserve or diminish the loss of muscle function. Therefore, the goal of this project is to examine the effects of essential amino acids alone or in combination with resistance or walking exercise on muscle protein metabolism, LBM and muscle function in older individuals. Hypothesis: The purpose of the study is to determine how the elderly's muscle and hormonal system respond to 10 days of bedrest. The study will also determine if amino acid (protein) supplementation and exercise can reduce muscle loss and maintain muscle function during 10 days of bedrest. Specific Aims and Procedures (summary): The importance of maintaining muscle mass and function after forced inactivity, such as illness, is clear. Information obtained from these studies will allow for a better understanding of the mechanisms involved in muscle protein metabolism in the elderly. This project will test two proven strategies that should reduce the loss of muscle mass and function in the elderly undergoing bedrest. Further, this project will investigate these strategies in terms of rehabilitation from inactivity and return to normal function. This project will help explain the metabolic mechanisms involved in response to exercise and nutrition. This information will be valuable for determining the optimal nutritional and exercise strategies to minimize the loss of muscle mass and function during hospitalization. These strategies are not only important for healthy individuals, but for those populations that will benefit from muscle growth, e.g., elderly, burn patients, astronauts, and those rehabilitating from serious injury or critical illness. Experimental Design (summary): We propose to study three groups of older men and women (65-80 years) before, during, and after 10 days of bedrest: 1) a group who will receive three supplements per day of EAA alone (EAA), 2) a group that will receive the same EAA supplementation plus three sessions of resistance exercise throughout bedrest (EAA+RE), and 3) a group who will receive EAA supplementation plus the standard-of-care daily walking exercise (EAA+WE). We will examine the hypotheses that the combination of EAA and these exercise regimens will be more effective in preserving muscle protein synthesis, LBM, and muscle function than either intervention alone. Further, we propose that combination of these interventions will expedite recovery from bedrest. Finally, we propose that these interventions, or combination of interventions, will be effective in maintaining muscle protein synthesis, muscle mass, and function in the elderly. Bedrest Study Timeline Study Visit Procedures Duration Screening visit one Blood tests, history, and physical 1-2 hr Screening visit two Heart station stress test 2-3 hr Study Days 1-4 (non-bedrest) Admission to GCRC Diet stabilization Strength testing Body composition testing Subjects at GCRC Study Day 5 1st Metabolic Study Study Days 6-8 Controlled metabolic diet Study Days 9-18 10 days' bedrest Study Day 18 2nd Metabolic Study Study Days 19-21 (non-bedrest) Strength testing Body composition testing PT and rehab sessions Bedrest ends on Day 19 Study Day 21 Discharge from GCRC - home Study Days 22-82 Rehabilitation program (up to 60 days) 60 min, 3 days/wk Significance (summary): Taken together, these findings demonstrate that the elderly have a higher likelihood of morbidity and mortality related to prolonged hospitalization and inactivity. There are several factors that contribute to the resulting loss of muscle mass and function: 1. For a given surgical procedure or injury, elderly patients require a longer period of hospitalization. 2. The elderly have an existing degree of insulin resistance that is exacerbated during physiological stress. 3. The elderly have less lean body and muscle mass than the young; therefore, a given loss of LBM has a greater impact on survivability, recovery, and function. 4. The elderly patient tends to be undernourished and this relates to length of hospital stay and outcome. Despite the proclaimed standard of care that attempts to get patients up and moving as quickly as possible after injury or surgery, the "reality" of care is that this does not often occur. Bedrest may not be prescribed for many maladies, but is inherent in the treatment of elderly patients. Attempts to adhere to the standard of care are thwarted by numerous factors, ranging from the inherent compromises of the aging physiology to economic and logistical issues. Given the dangers and risks of inactivity and bedrest on the elderly, it is vital that interventions be implemented to overcome these effects. We anticipate that the two interventions that were found, in our previous studies, to ameliorate the loss of LBM and muscle function in younger, bedrested volunteers will be effective at doing the same in the elderly. If this proves to be true, these interventions can be used to prevent or minimize loss of LBM and muscle function during periods of inactivity, which will improve and speed recovery thus having an enormous, positive impact for elderly individuals.