Oxidative damage, disability and mortality in elders

描述（由申请人提供）：行动障碍是老年人残疾过程的早期标志，是身体残疾和死亡的主要危险因素。然而，导致活动能力受限的病理生理机制在很大程度上仍然未知。氧化损伤通过破坏主要组成分子破坏生物系统的平衡，可能在导致重大健康相关事件的途径中发挥重要作用。有研究表明，氧化损伤、血小板活化和炎症是衰老过程中病理生理变化的促进因素，存在一个恶性循环。我们建议进行数据和生物样本分析，以评估氧化损伤和血小板活化标志物是否可以预测2345名健康衰老和身体成分研究中功能良好的人的行动障碍和死亡率的发生。次要目的是评估氧化损伤和血小板活化标志物与以下因素之间的关系：1)生物学因素（炎症、身体组成），2)行为因素（身体活动、体重增加、吸烟习惯），以及3)临床状况（心血管疾病、糖尿病、癌症、肺部疾病），这些因素可能介导活动能力障碍和死亡率的发生。拟议研究的结果将导致确定1)可能促进致残过程的机制，2)识别与健康相关事件风险的受试者的生物标记，3)新的潜在目标和候选干预措施，以预防行动能力，残疾和死亡率。

DESCRIPTION (provided by applicant): Mobility disability is an early marker of the disablement process in older adults, and represents a major risk factor for physical disability and mortality. However, pathophysiological mechanisms responsible for the onset of mobility limitation are still largely unknown. Oxidative damage, responsible for the disruption of the equilibrium of biological systems by damaging major constituent molecules, might play an important role in the pathway leading to major health-related events. It has been suggested the existence of a vicious cycle involving oxidative damage, platelet activation and inflammation as promoter of pathophysiological changes occurring with aging. We propose to conduct data and biological sample analyses to evaluate whether oxidative damage and platelet activation markers are predictors for the onset of mobility disability and mortality in 2,345 well- functioning persons enrolled in the Health Aging and Body Composition study. Secondary objectives are to evaluate the relationship of markers of oxidative damage and platelet activation with 1) biological factors (inflammation, body composition), 2) behavioral factors (physical activity, weight gain, smoking habit), and 3) clinical conditions (cardiovascular disease, diabetes, cancer, pulmonary disease) potentially mediating the onset of mobility disability and mortality. Results of the proposed study will lead to the identification of 1) mechanisms that may promote the disabling process, 2) biological markers that identify subjects at risk of health-related events, 3) new potential targets and candidates for interventions to prevent mobility disability and mortality.