Sleep, Aging and Circadian Rhythm Disorders

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DESCRIPTION (provided by applicant): Sleep in older people is marked by difficulty with initiation, frequent arousals, and early awakening. While the consequences of acute sleep deprivation have been investigated in older people, very little is known about the consequences of the chronic insufficient sleep experienced by many older people. Moreover, the interaction between the misalignment of circadian phase, so common in older people, and chronic insufficient sleep has not been studied. Our proposal seeks to address that gap in our knowledge by using a well-established laboratory model to study what differences may exist between the sleep efficiency of older and younger subjects under conditions of chronic sleep restriction (ratio 19 hours scheduled wake: 5 hours scheduled sleep), carried out on a forced-desynchrony protocol, and by assessing the recuperative capabilities under conditions of sleep extension following this restriction. The design of our human subjects protocol provides a tremendous opportunity to investigate an array of cognitive performance measures under these conditions of chronic sleep restriction and subsequent sleep extension. The Polysomnography Core of the proposed Program Project will provide accurate and reliable scoring of polysomnographic recordings from subjects participating in the experimental protocol as well as from prospective subjects during the screening process. A 'metabolic aging' experiment has been included in our proposal with the goal of understanding the endocrine and cardiovascular consequences of sleep restriction in both young and older subjects. In the previous cycle of this Program Project, it was hypothesized that sleep difficulties in older people might be due to loss of neurons in the ventrolateral preoptic nucleus (VLPO). A critical component of this proposal is the continued pursuit of this mammalian model for sleep regulation during aging. With aging, there is a loss of neurons in the ventrolateral preoptic nucleus (VLPO), which is necessary for normal sleep, with aging, and we hypothesize that rats with partial lesions of the VLPO are a high fidelity model for sleep in older people. We will test this model for its validity for older people by performing a series of studies that parallel the human components of this Program Project grant, both in older rats and in rats with partial VLPO lesions. We hypothesize that the VLPO lesioned rat is a good model for sleep in older people who have VLPO cell loss, and to use this model to test the efficacy of treatment designed to restore VLPO function, which we hope will restore sleep as well as improve cognitive and motor skills that deteriorate with aging and poor sleep. The core components - Administrative, Analytic and Polysomnography - are effective in providing support across projects and most importantly, providing for cohesion of efforts across the entire Program Project. The results of this research will have important implications for understanding the role of sleep in the health, safety, and neurocognitive functions of older people.