This proposal for an NIA SERCA: Nutritional Factors in Aging will provide expert-directed research experience for the Principal Investigator in design and conduct of patient-oriented research in nutrition and metabolism. The Principal Investigator has previously conducted basic research in lipid and lipoprotein biochemistry, and cell biology. He has recently trained in geriatrics and gerontology, and this NIA SERCA will extend his ability in patient-oriented research. The proposed studies are aimed at understanding mechanisms for metabolic abnormalities in cachexia, a syndrome which includes weight loss, hypoalbuminemia, hypocholesterolemia, anemia of chronic disease, and glucose intolerance. Cachexia is most prevalent in the very old and oldest old, is associated with decubitus ulcers, and is a risk factor for death. The interaction between nutrition, inflammation, metabolic abnormalities, and prognosis will be studied in immobile elderly with decubitus ulcers or at risk for developing decubiti. The primary hypothesis is that some metabolic abnormalities are due to inflammation and elevated cytokine levels, e.g. hypoalbuminemia; while other abnormalities are due to unmet requirements for energy intake, e.g. diminished fat mass. To test this hypothesis, nutritional variables (body composition, food intake, and energy expenditure), mediators of the acute response (plasma tumor necrosis factor alpha, interleukins 1beta and 6), and the non-specific indicator of T-cell activation, interleukin 2 receptor, and production of tumor necrosis factor alpha and interleukins 1beta and 6 by isolated monocyte macrophages will be measured. Two experimental designs will be employed: 1) a cross sectional study comparing subjects with decubiti with controls without decubiti, and 2) longitudinal studies of subjects with decubiti and subjects at risk for developing decubiti.
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