Candidate. The candidate, Kerrie L. Moreau, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Moreau's past and current research focus has been on physical activity, aging, and cardiovascular health, particularly in women. Her immediate goal is to acquire new research and professional skills to help her achieve her long-term goal of developing a successful independent extramurally-funded research program in aging. The proposed KO1 development plan should provide Dr. Moreau with the necessary training to achieve her goal. Career Development Plan. Dr. Moreau's research career development training activities consist of: 1) acquiring new research skills associated with and complimentary to (e.g., micro array gone expression analysis) the proposed research plan; and 2) structured activities including formal course work; attendance and presentation at journal clubs, seminar series, and scientific meetings; and regular interactions with her mentoring team. Environment. The environment for Dr. Moreau's training should be outstanding. The Sponsor and Co-sponsor, Drs. Douglas Seals and Wendy Kohrt, are well- established extramurally-funded scientists with strong records of successful mentoring in biomedical aging research. They are complimented by several consulting mentors who will provide guidance in specific areas of the training plan. Other faculty in aging research enhance the environment. Research. The general aim will be to determine the relative efficacy of 3 commonly used Hormone Replacement Therapy (HRT) regimens, regular aerobic exercise, and the combination of HRT and exercise for improving central (carotid) arterial compliance, the associated functional benefits, and the underlying mechanisms in healthy sedentary estrogen-deficient postmenopausal women. The general hypothesis is that HRT and exercise will, independently and additively, improve arterial compliance which will, in turn, result in functional benefits (e.g., improvements in cardiovagal baroreflex sensitivity and left-ventricular function/structure), and that these favorable adaptations will be mediated in part by a decrease in sympathetic tone (HRT only) and/or a reduced oxidative stress-associated improvement in vascular endothelium- dependent vasodilatory tone. Moreover, the amount of improvement with hormone supplementation and the additive effect of exercise will differ among HRT regimens. A 2-phase placebo controlled intervention trial employing state-of- the-art measurements of autonomic (e.g. micro neurography) and cardiovascular (e.g., high-resolution ultrasonography) function will be conducted. The expected results should provide new physiological and clinical information concerning the use of various HRT regimens and exercise for the primary prevention of reduced central arterial compliance with age and estrogen deficiency, the corresponding autonomic and cardiovascular functional benefits, as well as insight into the underlying mechanisms involved.
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