The overall objective is to test the hypothesis that age-related changes in the neuroendocrine system are potential biomarkers for mammalian aging. The focus of our research will be to study the decline in growth hormone secretory dynamics, plasma levels of somatomedin-C, and skeletal muscle protein synthesis as an integrated system. Previous research from our laboratory, and others, has clearly established that these variables decrease with age in rodents, monkeys and man. Administration of growth hormone has been shown to increase plasma levels of somatomedin-C in man, protein synthesis in rats, and immune function in several species with age. This comprehensive approach is designed to develop and verify a non-invasive index of neuroendocrine aging which will eventually be applicable to man. Our working hypothesis in developing an integrated approach to this area is that the age-related declines in protein synthesis and somatomedin-C are the result of a cascading effect initiated within the hypothalamic-hypophysial system. We will test this hypothesis by: (1) Assessing age-related changes in growth hormone secretory dynamics and plasma levels of somatomedin-C in 3 strains of rats and 4 strains of mice at 5 month intervals throughout the lifespan of these animals; (2) correlating measures described in (1) with the age-related decline in skeletal muscle protein synthesis and mean lifespan of the animal; (3) Determining the effects of dietary restriction on growth hormone, somatomedin-C, and protein synthesis; and (4) Assessing whether an increase in pituitary somatostatin receptors (recently observed by our laboratory in aging Fischer rats) is present in other aging rodents and is influenced by dietary restriction. To our knowledge there have been no studies of the growth hormone/ somatomedin- C system using moderate dietary restriction and this information is necessary to assess the role of these hormones as biomarkers of aging. The integrated/comprehensive approach of this application should provide data of high reliability (because of the inter- relationship between the measures) and validity (because of the use of several strains of rats/mice) on the relationship between the age-related decline in growth hormone and aging and its modification by dietary restriction.
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