Aging is associated with a gradual reduction in body protein content, primarily skeletal muscle. The significance of the maintenance of body protein balance is well recognized since loss of 30-50% of body protein is incompatible with life and protein depletion is a major factor in the morbidity of hospitalized patients. A recent retrospective analysis of serum albumin concentrations measured on admission to the Beth Israel Hospital in patients over the age of 65 yrs revealed a significant association between low albumin levels and hospital readmissions (Herrmann et. al.). Therefore, understanding factors which regulate body protein metabolism, especially in the elderly, is of considerable biological and clinical importance. The hypothesis to be examined in this proposal is that during aging, the interactions between energy and protein metabolism change in ways that may compromise the individual's ability to respond """"""""successfully"""""""" to physiologic and pathologic stress. Studies will utilize stable isotope tracer methodology, indirect calorimetry, and arteriovenous balance techniques to explore whole body and regional (skeletal muscle and liver) energy and amino acid (AA) metabolism in young (18-30 years) and old (65+ years) volunteers.
The specific aims of the proposal are: (1) To determine whether the relationship between resting metabolic rate (RMR) and protein turnover change with advancing age and to quantitate the contribution of skeletal muscle to differences in RMR and protein turnover in the old. (2) To examine the effect of insulin and AA availability on estimates of muscle protein turnover, O2 uptake and their inter- relationships. (3) To examine splanchnic AA metabolism in the aged; specifically, to determine whether there is an age-associated difference in fractional synthesis rates of specific hepatic proteins (albumin and apoprotein B). If the latter is true, a secondary specific aim is to determine whether age-related differences in energy expenditure (EE) or insulin sensitivity could account for these changes. (4) To determine the metabolic consequences of different energy-yielding nutrients, specifically fructose and glucose, on age-related differences in EE and protein/AA metabolism. Completion of these studies will further our understanding of nutritional factors which influence body protein and energy status and of the impact of body compositional changes in the integrity of protein metabolism and protein-energy interactions. Data obtained may aid in the development of specific dietary guidelines for the growing elderly population directed at minimizing morbidity and mortality.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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Massachusetts General Hospital
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