In humans and in rats, aging is associated with sleep disturbances, including frequent awakenings and stage changes. There is also a decreased circadian amplitude of the sleep/wake rhythm, reflected by more sleep during the normal active period and less sleep consolidation during the normal rest period. Whether the changes in sleep quality on the one hand, and in the distribution of sleep across the 24-hour cycle, on the other hand, are merely correlational or whether one causes or influences the other, is not known. The chronology of appearance of alterations in sleep quality and temporal distribution of sleep is also unknown, although human data indicate that decreases in slow-wave sleep already occur in early adulthood. Our overall goal is to determine the contribution of circadian timing to the development of sleep disturbance in the course of aging. Influences of circadian timing on sleep regulation could be exerted directly via efferent pathway(s) from the suprachiasmatic nucleus (SCN) or indirectly via SCN-driven rhythmicity of pineal function, a putative modulator of sleep/wake status. We will use a rodent model to fully characterize alterations in sleep across adulthood, both under baseline conditions, and when the system in stressed (by examining recovery sleep after sleep deprivation) using state-of-the-art techniques. Then we will determine the contribution of circadian timing to age-related changes in sleep quality and ability to recover from sleep deprivation by comparing young, middle-aged and older intact animals, SCN-lesioned animals and pinealectomized animals. This work will involve three technical advances: 1) we will use novel methods of quantitating sleep continuity; 2) we will make lesions using ibotenic acid (which is selective for cell bodies) rather than electrolysis (which damage fibers of passage); and 3) we will use the disk-over-water method of sleep deprivation. These studies will test the hypothesis that circadian rhythmicity plays a role in the deterioration of sleep and ability to recover from sleep loss in aging and will determine whether the effects of circadian timing are mediated by pineal secretory function (e.g. melatonin release).
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