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. Muscle mass and function progressively decline with aging. This process has been termed sarcopenia, and is associated with increased risk of falls and vulnerability to injury, especially bone fracture, which increase the risk of functional dependence. Our preliminary results suggest that there is a change in the response of muscle protein synthesis to insulin in the elderly, which can compromise the positive effect of amino acids on muscle protein gain. Our goal is to determine the mechanisms underlying the age-related insulin resistance of muscle proteins, which will allow us to define specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia. Subjects will be assigned randomly to any of the following groups: for 18-35 years old the possible groups are the following: insulin alone, insulin with L-NMMA, L-NMMA alone;meal;for 65 or older the possible groups will be the following: insulin alone, insulin with sodium nitroprusside;insulin with exercise;meal alone;meal with sodium nitroprusside;meal with exercise. We will measure the rate of metabolism, exchange, or turnover of amino acids in the body. Overall, we believe that this proposal will allow us to better delineate the changes in muscle metabolism with aging, thus providing a solid scientific basis for future intervention to prevent and treat muscle loss with aging (sarcopenia).
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