Oxidative stress links aging, activity, and mobility limitation

描述（由申请人提供）： 摘要：在美国退伍军人人口统计学揭示具有显著活动受限和氧化应激的老龄化人口与这两个特征密切相关的前提下，提出了一系列骨骼肌/血管研究。具体来说，在最近的一系列研究中，我们的团队记录了老年受试者在运动期间补充抗氧化剂的积极血管后果，对年轻人产生了负面影响。进一步的挑衅性研究结果显示，在运动训练后，老年受试者现在也受到抗氧化剂补充剂的负面影响。这些发现对理解运动康复、运动诱导的氧化应激、衰老、虚弱和随后的活动受限的积极影响之间的复杂平衡具有意义。因此，提出了四个具体的目标，将解决以下问题：1）急性运动诱导的氧化应激是更大的肌肉或血液随着年龄的增长？2)随着年龄的增长，对肌肉工作的哪种反应会产生氧化应激？3)随着年龄的增长，氧化应激的急性血管后果是什么？氧化应激在运动性血管适应中的作用。这项拨款提案的中心假设是，氧化应激是一种关键机制，可以操纵它来促进老年人运动的益处。 公共卫生相关性： 叙述：据估计，到2050年，超过21%的人将超过60岁，与此形成鲜明对比的是，退伍军人事务部的人口统计数据显示，51%（1230万）的退伍军人已经超过了这个年龄。通常情况下，随着年龄的增长，不活动，往往是移动限制。这已经并将越来越多地对VA医疗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，分别困扰30%和60%的退伍军人。前者仍然是美国退伍军人死亡的主要原因。这些过程之间的一个常见但尚未很好理解的联系是氧化应激。鉴于大量的老年退伍军人和衰老，不活动，氧化应激和致命的心血管疾病之间的明确联系，衰老和血管疾病已被适当地确定为VA医疗保健系统的医学研究重点。因此，这一提议的中心假设，即氧化应激是一种关键机制，可以被操纵，以促进老年人运动的好处是高度相关的VA患者护理使命。

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.