Aging and Sympathetic Vasoconstriction: Rest vs Exercise

描述(申请人提供)：候选人：候选人Frank A.Dinenno，Ph.D.，是一名生理学家，目前由NIA的一名个人NRSA支持。迪内诺博士之前和现在的研究重点都是交感神经对循环的控制，特别强调这些控制机制是如何随着年龄的增长和人类定期的体力活动而进行调节的。他的近期目标是获得新的研究和专业技能，以更好地准备和帮助他实现长期目标，即开发一个成功的独立、由外部资金资助的关于衰老和心血管功能的研究计划。拟议的KO1应该为Dinenno博士提供必要的培训，以实现他的目标。职业发展计划：Dinenno博士的研究职业发展培训活动将包括(1)获得与拟议的研究计划相关的新的研究技能，以及(2)与研究和专业技能相关的结构化活动。环境：迪内诺博士受训的环境将非常好。赞助商(乔伊纳博士)和咨询导师从事生物医学研究，并由NIH提供外部资金。所有人都是知名科学家，在生物医学研究方面有着成功的指导记录，六人中有三人是衰老研究方面的专家。综合临床研究中心的支持将改善培训环境。研究：将解决以下具体目标：1)确定在健康人的静息条件下，全腿α-肾上腺素能受体的反应性是否随着年龄的增长而降低，以及这是否对cq或c2-肾上腺素能受体具有特异性；(2)确定在大型肌肉动力运动中钝化肾上腺素能血管收缩的能力是否在老年人中受损，以及(3)这种损害是否是由于年龄相关的一氧化氮生物利用度降低所致；以及(4)确定定期有氧运动是否改善了先前久坐不动的老年人在休息和运动中钝化交感血管收缩的能力。预期的结果应该会产生关于老年人在休息和运动期间交感神经控制循环的新信息，而干预研究应该会产生关于老年人训练诱导的适应和外周循环控制的新信息。

DESCRIPTION (provided by applicant): Candidate: The candidate, Frank A. Dinenno, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Dinenno's previous and current research focus has been on sympathetic neural control of the circulation, with specific emphasis on how these control mechanisms are modulated by advancing age and regular physical activity in humans. His immediate goal is to acquire new research and professional skills to better prepare and help him achieve his long-term goal of developing a successful independent extramurally-funded research program on aging and cardiovascular function. This proposed KO1 should provide Dr. Dinenno the necessary training to achieve his goal. Career Development Plan: Dr. Dinenno's research career development training activities will consist of (1) acquiring new research skills associated with and complimentary to the proposed research plan; and (2) structured research- and professional skills-related activities. Environment: The environment for Dr. Dinenno's training will be outstanding. The Sponsor (Dr. Joyner) and consulting mentors are engaged in biomedical research and are extramurally-funded from NIH. All are established scientists with strong records of successful mentoring in biomedical research, three of the six are experts in aging research. Support from the General Clinical Research Center will enhance the training environment. Research: The following specific aims will be addressed: 1) to determine whether whole-leg alpha-adrenergic receptor responsiveness is reduced with age under resting conditions in healthy humans, and whether this is specific for cq- or c2-adrenergic receptors; (2) to determine whether the ability to blunt-adrenergic vasoconstriction during large muscle dynamic exercise is impaired in older adults and (3) whether this impairment is due to age-related reductions in nitric oxide bioavailability mediated via elevations in oxidative stress; and (4) to determine whether a program of regular aerobic exercise improves the ability of previously sedentary older adults to blunt sympathetic vasoconstriction at rest and during exercise. The expected results should yield new information regarding sympathetic neural control of the circulation at rest and during exercise in aging humans, and the intervention study should yield novel information about training-induced adaptations and peripheral circulatory control in older adults.