Oxidative damage, disability and mortality in elders

描述(由申请人提供)：行动不便是老年人致残过程的早期标志，也是导致身体残疾和死亡的主要风险因素。然而，导致运动受限的病理生理学机制仍然很大程度上不清楚。氧化损伤通过破坏主要组成分子来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。有人认为，随着年龄的增长，氧化损伤、血小板活化和炎症作为病理生理变化的促进剂，存在着恶性循环。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激活标志物是否可以预测参加健康老龄化和身体成分研究的2345名功能良好的人的行动障碍和死亡率的发生。第二个目标是评估氧化损伤和血小板激活的标志物与1)生物因素(炎症、身体成分)、2)行为因素(体力活动、体重增加、吸烟习惯)和3)临床条件(心血管疾病、糖尿病、癌症、肺部疾病)之间的关系，这些因素可能导致行动不便和死亡。拟议研究的结果将导致确定1)可促进残疾进程的机制，2)识别健康相关事件风险的生物标记物，3)新的潜在目标和干预措施，以防止行动不便和死亡。

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.