The present program project has the objective to delineate age-related changes in circadian rhythms, to determine their physiological mechanisms and functional significance and to examine the feasibility and efficacy of corrective strategies. The focus of the proposed animal studies is the understanding of the mechanisms by which aging affect the circadian system. The focus of the proposed human studies is to test the hypothesis that the senescence of the circadian system is partially responsible for age-related dysfunctions in systems driven by the clock. Our long-term goal is to improve the health and life quality of the elderly by improving nocturnal sleep, decreasing daytime sleepiness and re-establish the metabolic and endocrine correlates of a normal sleep- wake cycle. The project is a multidisciplinary and multi-institutional approach, combining non-invasive studies in subjects living in nursing homes affiliated with Northwestern University or the University of Chicago, clinical studies in older adults hospitalized in the Clinical Research Center of the University of Chicago, in vivo studies in hamsters and in vitro molecular studies in two laboratories at Northwestern University. The principal investigators and co-investigators have a long-standing history of successful collaborations in the area of circadian rhythms and have performed a number of independent studies related to the general theme of alterations in circadian timing during senescence. The present project will focus and coordinate a major portion of the research objectives of these laboratories on the chronobiology of aging. Project #1 will determine whether enforcement of a rigorous light-dark cycle and/or a structured social and activity schedule in nursing home residents will result in consolidated nocturnal sleep and improved daytime function. Project #2 will examine whether replacement of growth hormone in early sleep or restoration of elevated nocturnal melatonin levels, two hormonal events which are thought to act as internal synchronizers in young adults, may correct circadian rhythms alterations in older subjects. The objectives of Project #3 are to characterize in detail the effects of aging on the response of the hamster circadian clock to light and activity-inducing stimuli and to determine the physiological mechanisms underlying these effects. Project #4 will investigate the effects of aging on photic entrainment and on immediate early gene expression in the suprachiasmatic nuclei of old animals. These four Projects will be supported by three Cores. The Administrative Core will provide the overall logistical and financial coordination, assist in the recruitment of elderly volunteers and facilitate inter-institutional relationships as well as interactions between Projects and Investigators. The Methods and Analysis Core will supply, operate and maintain the equipment used in the four Projects to monitor circadian rhythms in humans and rodents and provide standard methods for reporting and analyzing temporal profiles of behavioral and physiological variables. The Clinical Core Laboratory will perform assays of hormones and peptides for Project #2 and centralize the screening and follow-up procedures for volunteers participating in Projects # 1 and #2.
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