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）：衰老与压力恢复能力降低有关，这是由于管理或从动态平衡的急性变化中恢复的能力降低。即使表面上健康，老年人遭受显着较差的结果相比，年轻人暴露于急性应激源，如疾病，受伤，或劳累。然而，老年人的反应是高度异质性的，这表明年龄本身并不是一个很好的预测结果。与老年人发病率和死亡率呈负相关的一个因素是身体健康。本研究将探讨体能对老化相关的两个领域的压力复原力的影响：氧化应激和神经内分泌应激反应。氧化应激被认为是衰老过程中的一个关键机制，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，并与年龄相关疾病的风险增加有关。毒物兴奋效应理论表明，一定量的压力可以导致更好的生存和减少组织损伤后，随后的压力。虽然急性运动是一种应激源，但定期运动训练会产生适应性反应，增加对连续运动应激的耐受性。据推测，与年龄相关的差异，在急性应激源的反应，从逐渐减少的能力，上调压力防御，以及温和的压力与适度的体力活动导致系统性的适应，防止或减弱这种下降的压力弹性与老化。为了测试身体健康是否为老年人提供了抵抗不同类型急性应激源的能力，我们将测量健康和不健康的老年男性和女性对两种急性应激源的反应;前臂缺血/再灌注（氧化应激）和心理社会实验室应激源（神经内分泌应激）。体能将由有氧能力（最大摄氧量）和峰值腿部力量决定。本研究的总体目标是提供增强的理解的机制，身体健康修改压力弹性在老年男性和女性。这项研究的结果可以增加我们对定期运动如何在衰老过程中带来益处的理解，并作为后续机制导向研究，运动干预研究和研究的试点数据，以可靠地评估饮食，生活方式和其他治疗方法，以增加风险增加的个体的抗压力能力。公共卫生相关性：对细胞和组织的氧化损伤增加以及应激激素的失调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病。采取干预措施，提高身体对压力的抵抗力，从而降低氧化应激，更好地调节应激激素，可以预防或延迟与年龄有关的疾病的发生，提高生活质量。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恢复力来实现。