The proposed San Antonio Center for Testing Aging Interventions will build upon the recognized strengths of UTHSCSA in biology of aging research. These include established cores for measuring longevity, life history traits and characterizing the pathologies and other aging biomarkers of mice under a wide spectrum of genetic, pharmacological and nutritional interventions. The three major goals of the center are: (1) to assess compounds that are hypothesized to slow aging and extend life span in rodents; (2) to identify those interventions that might be harmful or ineffective; and (3) to test hypotheses concerning mechanisms of aging through such trials. To achieve these goals, we propose the following specific aims: 1. To participate with other centers and NIA staff in the selection of compounds to be tested for their ability to promote healthy aging. 2. To perform pharmacokinetic and toxicological studies to determine appropriate starting doses for life-span studies in Phase I and II and for determining if doses in young animals are appropriate for older animals. 3. To perform Phase I life span studies, using genetically heterogeneous 4-way cross mice, with each selected compound at two doses. 4. To conduct gross end-of-life pathological analysis for all mice in Phase I studies and comprehensive end-of-life pathology for selected mice in Phase I and all mice in Phase II studies. 5. To conduct Phase II longevity and age-sensitive trait determinations for all compounds revealed from Phase I studies to have potential anti-aging action.
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