Oxidative stress links aging, activity, and mobility limitation

描述(由申请人提供)： 摘要：基于美国退伍军人的人口统计学特征显示人口老龄化具有明显的流动性限制，以及氧化应激与这两个特征密切相关的前提，提出了一系列骨骼肌/血管研究。具体地说，在最近的一系列研究中，我们的团队记录了在运动期间补充抗氧化剂对血管产生的积极影响，这对年轻人产生了负面影响。更具挑衅性的发现表明，在运动训练之后，年龄较大的受试者现在也受到抗氧化剂补充的负面影响。这些发现对于理解基于运动的康复的积极作用、运动引起的氧化应激、衰老、虚弱和随后的活动限制之间的复杂平衡具有重要意义。因此，提出了四个具体目标，以解决以下问题：1)急性运动引起的肌肉或血液中的氧化应激是否随着年龄的增长而增加？2)对肌肉工作的哪种反应会随着年龄的增长而产生氧化应激？3)氧化应激的急性血管后果是什么？4)氧化应激在运动诱导的血管适应中的作用。这项拨款提案的中心假设是，氧化应激是一种关键机制，可以通过操纵来为老年人类的锻炼带来好处。 公共卫生相关性： 叙述：在整个人口中，估计到2050年，超过21%的人将超过60岁，与之形成鲜明对比的是，退伍军人人口统计数据显示，51%(1230万)的退伍军人已经超过这个年龄。通常情况下，随着年龄的增长，人们会缺乏活动，而且往往行动不便。这已经并将越来越多地对退伍军人保健系统提出沉重的要求。此外，“血管老化”本身最近被认为是心血管疾病和高血压的主要危险因素，分别有30%和60%的退伍军人受到这两种疾病的困扰。前者仍然是美国退伍军人死亡的主要原因。氧化应激是这些过程之间的一种常见但尚未被很好理解的联系。鉴于退伍军人的数量众多，以及衰老、缺乏运动、氧化应激和致命性心血管疾病之间的明确联系，老龄化和血管疾病都被恰当地确定为退伍军人管理局医疗保健系统的医学研究重点。因此，这一建议的中心假设，即氧化应激是一种关键机制，可以被操纵来为老年人类运动的好处做出贡献，这与退伍军人管理局的患者护理任务高度相关。

DESCRIPTION (provided by applicant): ABSTRACT: With the premise that U.S. Veteran demographics reveal an aging population with significant mobility limitation and oxidative stress is tightly linked to both of these characteristics, a series of skeletal muscle/vascular studies are proposed. Specifically, in a series of recent studies our group has documented positive vascular consequences of antioxidant supplementation during exercise in older subjects that negatively impacted young people. Further provocative findings revealed that following exercise training the older subjects were now also negatively impacted by the antioxidant supplementation. These findings have implications for the understanding of the complex balance between the positive effects of exercise-based rehabilitation, exercise induced oxidative stress, aging, frailty, and subsequent mobility limitation. Therefore four specific aims are proposed that will address the following: 1) Is acute exercise-induced oxidative stress greater in muscle or blood with age? 2) Which response to muscular work generates oxidative stress with age? 3) What are the acute vascular consequences of oxidative stress with age? And 4) The role of oxidative stress in the exercise-induced vascular adaptations with age. The Central Hypothesis of this grant proposal is that oxidative stress is a key mechanism that can be manipulated to contribute to the benefits of exercise in aging humans. PUBLIC HEALTH RELEVANCE: Narrative: In the population at large it is estimated that by the year 2050 over 21% of people will be over 60 years of age, in stark contrast VA demographics reveal that 51% (12.3 million) of veterans are already over this age. Typically, with age comes inactivity and often mobility limitation. This has and will increasingly place heavy demands on the VA health care system. Additionally, "vascular aging" per se was recently recognized as a major risk factor for cardiovascular disease and hypertension which afflicts 30 and 60 % of veterans, respectively. The former continues to be the leading cause of death in U.S. veterans. A common, but as yet not well understood link between these processes is oxidative stress. Given the large number of older veterans and the clear link between aging, inactivity, oxidative stress, and lethal cardiovascular disorders, both aging and vascular disease have appropriately been identified as Medical Research Priorities for the VA health care system. Thus, the Central Hypothesis of this proposal that oxidative stress is a key mechanism that can be manipulated to contribute to the benefits of exercise in aging humans is highly relevant to the VA patient care mission.