AGING AND ADRENAL CATECHOLAMINE SYNTHESIS AND SECRETION

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A three-year career development plan is presented that will allow me to make a successful transition into conducting state-of the- art, extramurally funded aging research. With Dr. Phyllis M. Wise as my mentor, this plan will consist of a series of intensive training experiences with established investigators in the aging arena at the University of Kentucky. This training will allow me to develop a high level of expertise in electrophysiology (with Drs. McMahon and Landfield) and in molecular biology (with Drs. Wise and Estus), two areas in which I have relatively little experience, but which will be critical for both the successful completion of the studies proposed in this application as well as for the design and execution of future aging specific projects. In addition, I will receive training in confocal laser scanning microscopy with Dr. Mattson, which will dramatically enhance my current expertise in fluorescent imaging of intracellular Ca2+ dynamics. Experimentally, I will use chromaffin cells in short-term culture to test the hypothesis that the increased rate of adrenal medullary catecholamine secretion that occurs in aged subjects is the result of changes in nicotinic receptor-dependent increases in intracellular Ca2+ signaling via voltage-gated Ca2+ channels. The data derived from these studies will be incorporated into a comprehensive RO1 application that will be submitted toward the end of the training period. My long-term career objective is to maintain a vigorous, nationally and internationally respected research program in aging. This career development plan, coupled with the enormous wealth of aging-related research and academic resources that are available at the University of Kentucky, will allow me to achieve this objective.