This Program Project is one of two studies which asks: Can dietary restriction (DR), long known to retard aging and diseases in rodents, do so in non-human primates? Our hypothesis is that DR will similarly retard aging in a primate species, as reflected by attenuated rates of change of most biological indicators of aging, delayed diseases and increased longevity.
Two Specific Aims will continue to be addressed. Ap.
Aim 1 is to contribute to the development of the rhesus monkey (Macaca mulatta) as a model for the study of aging. An improved understanding of biological aging and its longitudinal measurement is needed in this species. Ongoing study of conventionally-fed animals from our large aging colony will be continued as will investigation of three Cohorts of DR and Control rhesus monkeys, all of which were young adults (approximately 10 years old) when entering the study. Cohort 1 (n=15/group, males) which are being followed as per Cohort 1; and Cohort 3 (n=8, males) had undergone surgical biopsies to provide tissues (e.g., liver, spleen) well-studied in rodents on DR. These three Cohorts are allowing us to address Sp.
Aim 2 : to determine the influence of DR on the rate of aging in a primate species. Our structurally uncomplicated project has interdependent components. The projects depend entirely on Procurement""""""""). In response to reviewer concerns, we have improved these Cores by increasing biostatistical support and revamping the studies on biomarkers of aging as well as by minimizing the frequency and intensity of testing in these valuable animals. A linking theme is energy metabolism and balance because the magnitude of DR's effects in rodents parallels the level of energy intake. We hypothesize that adjustments of energy and free radical metabolism are major mechanisms in DR's ability to retard aging. The project """"""""Role of Oxidative Stress of Mitochondrial Origin in Sarcopenia"""""""" expands our P01-supported mechanistic studies on this topic. Another project """"""""Energy Balance and Substrate Metabolism"""""""" will continue to probe relationships among DR, body composition and fat distribution, and energy expenditure as well as to investigate carbohydrate and lipid metabolism. Finally, a new Project """"""""Quantitative Analysis of Immunity to Viral Immunogens"""""""" is proposed which, to our knowledge, will be the first to study immune responses in this species at molecular and cellular levels in the context of energy restriction. Thus, we propose to use the outstanding Primate Center resource to continue addressing a question at the heart of the biology of aging and of interest to a significant segment of the general populace.
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