Oxidative damage, disability and mortality in elders

描述（由申请人提供）：行动不便是老年人残疾过程的早期标志，是身体残疾和死亡的主要风险因素。然而，导致活动受限的病理生理机制在很大程度上仍然是未知的。氧化损伤通过破坏生物系统的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。已经表明存在一个恶性循环，涉及氧化损伤、血小板活化和炎症，作为随着衰老发生的病理生理变化的促进剂。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是参与健康老化和身体组成研究的2,345名功能良好的人中发生移动性残疾和死亡的预测因子。次要目的是评价氧化损伤和血小板活化标志物与1）生物学因素（炎症、身体组成）、2）行为因素（体力活动、体重增加、吸烟习惯）和3）可能介导移动性残疾和死亡发生的临床状况（心血管疾病、糖尿病、癌症、肺部疾病）的关系。拟议研究的结果将导致识别1）可能促进残疾过程的机制，2）识别健康相关事件风险受试者的生物标志物，3）预防移动性残疾和死亡的干预措施的新的潜在目标和候选人。

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.