MANIPULATIONS OF INTERNAL ZEITGEBERS IN THE ELDERLY

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In older adults, nocturnal sleep is often shallow and fragmented and this is associated with decreased daytime alertness. The timing of sleep is also modified, with earlier bedtimes and morning awakenings. Earlier timing and reduced amplitude have also been observed for other 24-hour rhythms, including those of hormonal secretions. These alterations are thought to reflect age-related changes i the brain mechanisms controlling circadian rhythmicity and/or the sleep/wake state. These two systems interact, as circadian rhythmicity modulates the timing and duration of sleep and the sleep-wake cycle in turn exerts synchronizing (i.e. zeitgeber) effects on the circadian pacemaker. The other major zeitgeber for circadian rhythmicity is the light-dark cycle. Recent research has indicated that age-related alterations in exposure and response to non- photic and photic zeitgebers may be more severe than alterations in intrinsic pacemaker function and/or chronologically precede such alterations. The present project will: 1. test the hypothesis that decreases in both non-photic inputs (slow-wave activity and ability to recover from sleep loss) and photic inputs (diminished melatonin suppression and/or reduced ability to phase-shift in response to light exposure) may be already present in midlife and contribute to the development of alterations of circadian rhythmicity, sleep and endocrine function in late life; 2. explore strategies designed to restore exposure to non-photic inputs (by restoring slow-wave activity and the associated GH secretion and photic inputs (by restoring nocturnal melatonin levels similar to those observed in young subjects using a transmucosal melatonin patch applied to th gum) to correct alterations of circadian rhythmicity, sleep and endocrine function in midlife and late life. These studies will test the hypothesis that the senescence of the sleep and/or circadian systems in partially responsible for age-related dysfunctions in hormonal secretions, delineate the earliest alterations in the circadian/sleep systems occurring in course of aging and provide information regarding athe feasibility and efficacy of preventive or corrective strategies.