Aging: Effects on Infection, Inflammation and Disease

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DESCRIPTION (provided by applicant): This proposal is a collaborative submission from the University of Kentucky, the University of Maryland, and the Nutritional and Molecular Physiology Unit of the Laboratory of Neurosciences of the National Institute on Aging. The proposed studies will build on existing data obtained from Rhesus monkeys being maintained on calorie restricted and normal diets by the NIA, and will provide a biologic basis for our preliminary observations of altered inflammatory responses in calorie restricted animals. This proposal focuses on utilizing the oral cavity as a model system to examine the impact of aging on host-bacterial interactions as they relate to microbial colonization of mucosal surfaces, the induction and regulation of inflammatory/immune responses, and the pathologic destruction of host tissues that may result from these interactions. The aims of this study will test the following contrasting scientific hypotheses: (a) that caloric restriction (CR) reduces clinical inflammation by affecting the pathogenicity of microbial plaque, and that these changes are due to shifts in the proportions and/or clonal type of the constituent pathogenic and non-pathogenic microorganisms; (b) that CR alters the clinical manifestation of inflammation through an effect on innate immune mechanisms through increased pro-inflammatory molecule release; and/or (c) that CR alters the clinical manifestation of inflammation through an effect on innate immune mechanisms by regulating the release of anti-inflammatory molecules. Aim 1 is a cross-sectional retrospective study to determine the effects of a long-term calorie restricted diet on the progression of naturally occurring inflammatory periodontal disease in CR and non-CR Rhesus monkeys. The effects of CR on clinical inflammation, microbial colonization of mucosal surfaces, and pro-inflammatory and anti-inflammatory mechanisms will be evaluated. Aim 2 is a longitudinal prospective study to determine the effects of a calorie-restricted diet on the clinical, microbiological, and host responses observed during experimental ligature-induced periodontitis in the same CR and non-CR Rhesus monkeys. These studies will provide information on the effects of CR on the kinetics of clinical, microbiologic, and inflammatory changes at mucosal sites. The significance of these studies lies in our capability to use nonhuman primates and the oral cavity to evaluate the efficacy of CR as a means to regulate infection, inflammation, and inflammatory disease. The long-term implications are that diet control may be considered as an effective public healthcare measure for improving the oral and general health and welfare of the population as a whole.