Growth Hormone, Angiotensin II, and Cardiac Aging

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The candidate for the Paul B. Beeson Career Development Award in Aging was awarded the M.D. degree and received post-graduate fellowship training in cardiothoracic anesthesiology. The candidate has chosen to combine her cardiovascular background and interest in aging to study mechanisms of diastolic dysfunction related to aging. To this end, the candidate participated in the NIA Summer Research Institute and was subsequently awarded an R03 and the Dennis Jahnigen Career Development Award to examine the role of Insulin-like Growth Factor-1 (IGF-1) in Diastolic Dysfunction, which is the basis for the current career development plan. The proposed award will enable the candidate to accomplish the following objectives: 1) expand her scientific knowledge and research techniques in aging; 2) define a potential mechanism of diastolic dysfunction of aging; and 3) allow the candidate to independently plan and conduct basic research in aging. The research plan will facilitate the candidate's accomplishment of these goals by providing opportunities for advanced education in the physiology of aging, molecular and cellular biology, statistics, and a seminar on responsible conduct in research. The candidate will be directed in her efforts by an interdisciplinary group of investigators in hypertension, cardiology, physiology and pharmacology. Opportunities will be available for the candidate to present and discuss research in progress with young investigators affiliated with the Hypertension Center and the J. Paul Sticht Center of Aging and Rehabilitation. Within this environment, the candidate will characterize age-related changes in circulating and intracardiac renin-angiotensin (RAS) systems as they relate to the structural and functional changes in the aged rodent heart. The contribution of GH/IGF-1 senescence to diastolic dysfunction and the balance of RAS, specifically ACE and ACE2, will be explored. The functional role of RAS in the control of cardiac remodeling and diastolic performance will be examined using RAS-inhibition and GH supplementation. This award will provide a foundation for the development of the candidate as an independent clinician-investigator in aging, and the study results will ultimately contribute to improvement of the care of the elderly patient.