Oxidative damage, disability and mortality in elders

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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.