Center for Testing Potential Anti-Aging Interventions

The NIA Interventions Testing Program represents a multi-site translational research program to evaluate agents hypothesized to extend mouse lifespan by retardation of aging or postponement of late life diseases. Interventions proposed by multiple collaborating scientists from the research community are initially tested, in parallel, atthree sites (Jackson Laboratories, Michigan and Texas), using identical, standardized protocols, and using sufficient numbers of genetically heterogeneous mice to provide 80% power for detecting changes in lifespan of 10%, for either sex, after pooling data from any two of the test sites. Forty such lifespan experiments, involving various doses of 25 distinct agents, have been initiated in the first nine years of the ITP. Significant effects on longevity, in one or both sexe, have been documented for 5 of the tested agents: aspirin, NDGA, rapamycin, acarbose, and 17-?-estradiol. Initial lifespan trials are now underway for 8 agents, as well as comprehensive analyses of the effects of rapamycin, acarbose, and NDGA on health and on cellular and physiological traits thought likely to mediate the beneficial effects seen. Plans for the next five year period include additional lifespan ('Stage I') trials, detailed analyses ('Stage II') of agent found to increase lifespan, and increased emphasis on collaborations with other scientists skilled at evaluating traits related to health and disease or at testing ideas about mechanisms of drug action on aging. Each of the three ITP laboratories will bring special expertise to the effort measures of age-sensitive traits at the Jackson Laboratory, pathology and statistical analysis at Michigan, and pharmacology at the University of Texas. PUBLIC HEALTH RELEVANCE: The NIA Interventions Testing Program represents a multi-site translational research program to evaluate agents hypothesized to extend mouse lifespan by retardation of aging or postponement of late life diseases. If successful, the work of the ITP consortium and its collaborators will lead to two kinds of progress: 1) it will yield new insights into the control of aging, aging rate, and age-associated diseases, and generate new mouse models to support work on these topics throughout the scientific community; and 2) it may help to facilitate the eventual development of agents that could be of benefit in preventive medicine, either by disrupting links between aging and disease, or by retardation of multiple diseases through decelerating the aging process itself.