Core Facility for Aged Rodents

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Abstract The principal goal of the Core Facility for Aged Rodents (CFAR) is to develop new mouse models that can be used to evaluate the physiological and cellular factors that control the rate of aging and tie aging to late-life diseases. New mouse models are often suggested by other scientists, at UM or at other institutions, and these are evaluated as potential collaborations. CFAR resources are used for initial characterizations, often including studies of lifespan, age-sensitive indices of health, and pathology, with a view towards producing sufficient data to allow the new mouse models to be used in competitive applications for extramural support. In keeping with the overall theme of the UM OAIC, many of the mouse systems developed depend on alterations of metabolic and/or inflammatory pathways, whether by genetic changes, dietary interventions, or, more recently, drugs. The specific mutants, diets, or drugs chosen each year depend on scientific discoveries and interactions in each preceding year. Specific Aims: Aim 1 will support six externally funded projects (EPs) in year 1, including work on serotonin receptor mutants, drug effects on gene expression patterns, effects of anti- aging drugs on cancer cells, work on cap-independent translation of specific mRNAs, studies of adipose tissue inflammation, and an analysis of over-expression of an enzyme that protect mitochondria from oxidative damage. Aim 2 uses CFAR resources to maintain breeding colonies of special interest to mouse aging research, including mutants with tissue-specific alterations in Growth Hormone receptor, the IGF1 binding protein protease PAPPA, the mitochondrial redox protecting enzyme thioredoxin reductase 2, and two proteins that promote cap-independent translation of mRNA subsets. Aim 3 focuses on training, consultation, and professional education, so that CFAR can provide sophisticated perspectives on mouse aging models to PES and REC applications, and to UM students, fellows and faculty, and contribute to development of national standards for optimal use of rodents in biogerontology. Aim 4 involves selection of one or two new innovative mouse models for development in each year of the award. CFAR has, since its inception in 1989, provided both local and national leadership in the development of new mouse models for research on the control of aging and its links to late-life diseases, and hopes to maintain this role in the next award period.