PHYSICAL PERFORMANCE AND LONGEVITY IN AGED MICE

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

DESCRIPTION (provided by applicant): This proposal represents an extension of a previous OAIC project that established the face validity of a model designed to evaluate physical performance decline in aged rats. The rationale for this previous project related to the utilization of methods in rats that are conceptually similar to those currently used in humans to assess physical performance before the appearance of overt disabilities, and to determine whether individual variations in these measures predict future disability and mortality. This approach allows for early identification of high-risk individuals who would most benefit from preventive interventions. The specific goal of the current proposal is to extend this approach to assess physical performance in mice. The application of standardized physical performance measures to these models will help to define the underlying mechanisms of age-related decline in performance. Most importantly, these standardized assessments will be used for pre-clinical testing of novel interventions designed to prevent age-related physical function decline. We consider this approach to be innovative, given that new interventions to prevent disability are currently tested directly in humans, with no pre-clinical testing in animal models that reflects the conditions under which these interventions would be administered as preventive or curative agents. The purpose of this application is to extend our development of a translational model of physical performance assessment to include mice as subjects and to more fully characterize age-related changes in physiological and biochemical parameters that correlate with declining function. We hypothesize that 1) decline in performance ability can be measured longitudinally in the latter phases of the aging process, when there are sharp declines in function and viability; 2) poor performance at baseline on one or more measures (or a composite of these measures) will predict reduced longevity compared to more optimal performers; 3) age-related declines in muscle fiber contractility, loss of muscle mass, and increased level of circulating cytokines are highly correlated with poor physical performance, and will predict longevity in longitudinal studies. Extending this analysis to mice will provide a basis in the future for assessing the impact of a specific factor or characteristic on the disabling process by taking advantage of special knockout and transgenic models that are relevant to the study of aging.