Systemic and Localized Stress Resilience in Aging: Effects of Physical Fitness.

衰老过程中的全身和局部压力恢复能力：身体健康的影响。

• 批准号: 7622581
• 负责人: TINNA TRAUSTADOTTIR
• 金额: $ 5.67万
• 依托单位: KRONOS LONGEVITY RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2011-01-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622581
• 关键词: Acute; Aerobic; Age; Aging; Aging-Related Process; Alzheimer' s Disease; Antioxidants; Area; Atherosclerosis; Attenuated; Cardiovascular Diseases; Cells; Chronic; Chronic Disease; Corticotropin; Data; Disease; Elderly; Excretory function; Exercise; Exertion; F2-Isoprostanes; Fibrinogen; Forearm; Homeostasis; Hormones; Hydrocortisone; Individual; Injury; Intervention; Intervention Studies; Ischemia; Laboratories; Lead; Leg; Life Style; Link; Lipids; Malignant Neoplasms; Measurement; Measures; Morbidity - disease rate; Neurosecretory Systems; Nucleic Acids; Operative Surgical Procedures; Outcome; Oxidative Stress; Oxidative Stress Pathway; Oxygen Consumption; Pathologic Processes; Physical Fitness; Physical activity; Pituitary-Adrenal System; Plasma; Play; Production; Proteins; Protocols documentation; Psychosocial Stress; Quality of life; Reactive Oxygen Species; Regulation; Reperfusion Therapy; Resistance; Rest; Risk; Role; Salivary; Serum; Stimulus; Stress; Testing; Therapeutic; Tissues; Training; Urine; Woman; Workload; acute stress; adduct; age effect; age related; biological adaptation to stress; disability; fitness; follow-up; hypothalamic-pituitary-adrenal axis; improved; mortality; older men; oxidative damage; prevent; psychosocial; public health relevance; response; stress resilience; stressor; theories; tool; urinary; young adult

DESCRIPTION (provided by applicant): Aging is associated with reduced stress resilience due to diminished ability to manage or recover from acute changes in homeostasis. Even apparently healthy, older adults suffer dramatically poorer outcomes compared to young adults when exposed to acute stressors such as illness, injury, or exertion. However, the response in older individuals is highly heterogeneous, suggesting that age alone is not a good predictor of outcome. One factor that inversely correlates with morbidity and mortality in older adults is physical fitness. This study will investigate the effects of physical fitness on stress resilience in two areas related to aging: oxidative stress and neuroendocrine stress reactivity. Oxidative stress is believed to be a key mechanism in the aging process, and is implicated in many pathological processes. Similarly, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to play a role in aging and is linked to the increased risk for age-related disease. The hormesis theory suggests that a certain amount of stress can lead to better survival and reduced tissue damage following subsequent stress. While acute exercise is a stressor, regular exercise training results in adaptive responses that increase the tolerance for successive exercise stress. It is hypothesized that age-related differences in the response to acute stressors arise from a gradually diminished ability to up-regulate stress defenses, and that the mild stress associated with moderate physical activity leads to systemic adaptations that prevent or attenuate this decrease in stress resilience with aging. To test whether physical fitness provides older individuals with increased ability to resist disparate types of acute stressors, we will measure the response of fit and unfit older men and women to two acute stressors; forearm ischemia/reperfusion (oxidative stress), and a psychosocial laboratory stressor (neuroendocrine stress). Fitness will be determined by aerobic capacity (VO2 max) and peak leg power. The overall aim of this study is to provide enhanced understanding of the mechanisms by which physical fitness modifies stress resilience in older men and women. The results from this study can increase our understanding of how regular exercise confers its benefits on the aging process and serve as pilot data for follow-up mechanistic-oriented studies, exercise intervention studies, and studies to reliably evaluate dietary, lifestyle, and other therapeutic approaches to increase stress resistance capacity in individuals at increased risk. Public Health Relevance: Increased oxidative damage to cells and tissues and dysregulation of stress hormones have been linked to age-associated chronic diseases including atherosclerosis, cancer, cardiovascular disease and Alzheimer's disease. Interventions to improve the body's resistance to stress, resulting in lower oxidative stress and better regulation of the stress hormones, may prevent or delay the onset of age-related diseases and improve quality of life. The well-known benefits of regular exercise training in reducing the risk for chronic diseases may partly occur through modulation of oxidative stress pathways and better stress resilience.

描述（由申请人提供）：衰老与降低的压力弹性有关，由于稳定​​稳态的急性变化能力降低或恢复。与年轻人相比，与年轻人相比，即使是健康的老年人，在疾病，受伤或劳累等急性压力时，结果也差得多。但是，老年人的反应是高度异质的，表明仅年龄并不是结果的良好预测指标。与老年人的发病率和死亡率成反比的一个因素是身体健康。这项研究将研究身体适应性对与衰老有关的两个领域的应激弹性的影响：氧化应激和神经内分泌压力反应。氧化应激被认为是衰老过程中的关键机制，并且与许多病理过程有关。同样，下丘脑 - 垂体 - 肾上腺（HPA）轴的失调被认为在衰老中起作用，并且与与年龄相关疾病的风险增加有关。激素理论表明，一定程度的压力会导致更好的存活，并在随后的压力后减少组织损伤。尽管急性运动是压力源，但定期的运动训练会导致自适应反应，从而增加了连续运动压力的容忍度。假设与年龄相关的对急性应激源的反应差异是由于逐渐下调压力防御能力的能力逐渐下降，并且与中等身体活动相关的轻度压力会导致全身适应性，从而可以预防或减轻与年龄相关的压力恢复的降低。为了测试身体适应性是否为老年人提供了抗抑郁类型的急性压力源的能力，我们将衡量适合和不适合老年男女对两个急性压力源的反应；前臂缺血/再灌注（氧化应激）和社会心理实验室压力源（神经内分泌压力）。健身将由有氧运动能力（VO2 MAX）和峰值腿部功率确定。这项研究的总体目的是增强人们对身体适应性修饰老年男性和女性压力弹性的机制的理解。这项研究的结果可以提高我们对定期运动如何在衰老过程中的益处的理解，并充当试点数据，以进行随访的机械性研究，运动干预研究和研究，以可靠地评估饮食，生活方式和其他治疗方法，以增加风险增加个人的个人压力抗性能力。公共卫生相关性：对细胞和组织的氧化损害增加以及压力激素的失调与与年龄相关的慢性疾病有关，包括动脉粥样硬化，癌症，心血管疾病和阿尔茨海默氏病。改善人体抵抗压力的干预措施，导致较低的氧化应激和更好的压力激素调节，可以防止或延迟与年龄有关的疾病的发作并改善生活质量。定期运动训练在降低慢性疾病风险方面的众所周知的好处可能部分通过调节氧化应激途径和更好的压力弹性而发生。