GRANT=6423578;P01AG This application seeks renewed support for the Program Project in Biomedical Outcomes of Aging. We hypothesize that age-associated growth hormone declines influence cardiac and peripheral muscle function during congestive heart failure compensation. Finally, we hypothesize that age-related decrements in insulin release and action lead to the glucose intolerance of aging. Building on our preliminary observations we have formulated a common hypothesis that trophic factor restoration (employing exogenous agents?GHRH, testosterone, GLP/Exendin) will not only correct the underlying deficiency states but be useful tools to correct the impaired tissue structure or function, and improve the symptoms of functional loss in settings where tissue related illnesses have resulted (CHF, sarcopenia and diabetes mellitus). On a more fundamental level we will explore the mechanisms underlying correction of the """"""""trophic endocrinopathy of aging."""""""" Protein synthesis in the heart, peripheral muscle metabolism, growth factors, and hormonal release and action will all be examined before and after hormonal substitution. Common study designs of hormone replacement protocols will be employed to examine structural and functional changes. The shared resources and scientific collaborations int his renewal encompass data management, common analytical procedures (e.g. radioimmunoassays, body composition analysis) and a supply-purchasing system. The Program Project also forms an excellent forum for training of gerontologic investigators, particularly Ph.D. and M.D. trainees entering our institutional programs. The relocation The relocation of the Program Project to the Massachusetts General Hospital following the Principal Investigator's move and the establishment Medicine Unit at the Massachusetts General Hospital opens and extends collaborations. Our new MGH collaborator is Dr. Laurence Katznelson, Endocrine Division. The extensions are Dr. Joel Habner, collaborator of Drs. Elahi and Minaker for many years,"""""""" and Dr. Ronenn Roubenoff Joseph Kehayias and Ms. Virginia Hughes at the USDA Human Nutrition Research Center on Aging at Tufts University. The significance of each project rests in its contribution to the understanding of physiologic and pathophysiologic mechanisms relevant to the health and the common diseases affecting aging Americans.
