MANIPULATIONS OF INTERNAL ZEITGEBERS IN THE ELDERLY

在老年人中，夜间睡眠通常是浅而零碎的，这 与白天警觉性下降有关。睡眠的时间是 也进行了修改，提前了就寝时间和早晨的起床时间。早些时候 在其他24小时内也观察到了定时和幅度降低 节律，包括激素分泌的节律。这些改动是 反映年龄相关变化的思想--大脑控制机制 昼夜节律性和/或睡眠/清醒状态。这两个系统 相互作用，因为昼夜节律性调节时间和持续时间 睡眠和睡眠-觉醒循环依次施加同步(即 Zeitgeber)对昼夜节律起搏器的影响。另一个主要的时代潮流 因为昼夜节律性是明暗循环。最近的研究表明 表明与年龄相关的暴露和对非 光和光的沸石可能比变化更严重 内在起搏器功能和/或时间顺序先于此 改装。本项目将：1.检验假设 非光输入减少(慢波活动和 从失眠中恢复)和光输入(褪黑素减少 抑制和/或降低响应光的相移能力 暴露)可能已经出现在中年，并有助于 昼夜节律、睡眠和内分泌变化的研究进展 晚年生活中的功能；2.探索旨在恢复暴露的策略 至非光输入(通过恢复慢波活动和相关的生长激素 分泌和光输入(通过恢复夜间褪黑激素水平 类似于在年轻受试者身上观察到的跨粘膜褪黑素 贴在牙床上)以纠正昼夜节律的改变， 睡眠与中老年的内分泌功能。这些研究将 测试睡眠和/或昼夜节律衰老的假设 荷尔蒙中与年龄相关的功能失调的部分机制 分泌物，描绘了昼夜节律/睡眠的最早变化 系统在老化过程中发生的情况，并提供有关 预防或纠正策略的可行性和有效性。

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.