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: 7470516
• 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 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470516
• 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; Localized; 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; Physiological reperfusion; Pituitary-Adrenal System; Plasma; Play; Production; Proteins; Protocols documentation; Psychosocial Stress; Public Health; Quality of life; Reactive Oxygen Species; Regulation; Reperfusion Therapy; Resistance; Rest; Risk; Role; Salivary; Serum; Stimulus; Stress; Testing; Therapeutic; Thinking; Tissues; Training; Urine; Woman; Workload; acute stress; adduct; age effect; age related; biological adaptation to stress; day; disability; fitness; follow-up; hypothalamic-pituitary-adrenal axis; improved; mortality; older men; prevent; psychosocial; 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）：由于管理或从体内平衡的急性变化中恢复的能力下降，衰老与压力恢复能力降低有关。与年轻人相比，即使是表面上健康的老年人，在暴露于疾病、受伤或劳累等急性压力源时，其结果也要差得多。然而，老年人的反应是高度异质性的，这表明年龄本身并不能很好地预测结果。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。本研究将从氧化应激和神经内分泌应激反应两个与衰老相关的领域探讨体能对应激恢复能力的影响。氧化应激被认为是衰老过程的关键机制，并涉及许多病理过程。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。激效理论表明，一定程度的压力可以导致更好的生存，减少后续压力带来的组织损伤。虽然急性运动是一种应激源，但定期运动训练可以产生适应性反应，增加对连续运动应激的耐受性。据推测，对急性应激源的反应中与年龄相关的差异源于应激防御能力的逐渐减弱，并且与适度体育活动相关的轻度应激导致系统适应，从而防止或减弱这种随年龄增长而下降的应激恢复能力。为了检验身体健康是否能提高老年人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）和社会心理实验室应激源（神经内分泌应激）。体能将由有氧能力（最大摄氧量）和最大腿部力量决定。本研究的总体目的是为了更好地理解身体健康改变老年男性和女性压力恢复能力的机制。这项研究的结果可以增加我们对规律运动如何在衰老过程中带来好处的理解，并作为后续机械导向研究、运动干预研究、可靠评估饮食、生活方式和其他治疗方法的研究的试点数据，以提高风险增加的个体的抗压能力。公共卫生相关性：细胞和组织氧化损伤的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。通过干预措施提高身体对压力的抵抗力，降低氧化应激，更好地调节应激激素，可以预防或延缓与年龄有关的疾病的发生，提高生活质量。众所周知，定期运动训练在降低慢性疾病风险方面的好处，可能部分是通过调节氧化应激途径和更好的应激恢复能力来实现的。