MANIPULATIONS OF INTERNAL ZEITGEBERS IN THE ELDERLY

老年人内部时间的操纵

• 批准号: 6098500
• 负责人: Eve Van Cauter
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6098500
• 关键词: age difference; attention; blood chemistry; body physical activity; body temperature; circadian rhythms; clinical research; endocrine pharmacology; hormone regulation /control mechanism; hormone therapy; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; melatonin; neuropsychological tests; outcomes research; performance; photostimulus; sleep; sleep disorders; somatotropin; wakefulness; young adult human (21-34)

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.

在老年人中，夜间睡眠通常是浅的和碎片化的， 与日间警觉性下降有关。 睡眠的时间是 也修改了，早睡早起。 早些时候 在其他24小时内也观察到了时间和幅度的减少 节奏，包括荷尔蒙分泌的节奏。 这些变化是 被认为反映了大脑机制中与年龄相关的变化， 昼夜节律和/或睡眠/觉醒状态。 这两个系统 相互作用，因为昼夜节律调节的时间和持续时间 睡眠和睡眠-觉醒周期依次施加同步（即， Zeitgeber）对昼夜节律起搏器的影响。 另一个主要的时代性 昼夜节律就是明暗循环。 最近的研究 表明，年龄相关的变化，暴露和反应，非- 光和光授时因子可能比光的改变更严重， 内在起搏器功能和/或在时间上先于这些功能 改变。 本项目将：1. 测试的假设 两种非光输入（慢波活动和 从睡眠缺失中恢复）和光输入（褪黑激素减少 抑制和/或降低响应于光相移的能力 暴露）可能已经存在于中年，并有助于 昼夜节律、睡眠和内分泌发生改变 在晚年的功能; 2. 探索旨在恢复暴露的策略 到非光输入（通过恢复慢波活动和相关的GH 分泌和光输入（通过恢复夜间褪黑激素水平 类似于在使用经粘膜褪黑激素的年轻受试者中观察到的那些 贴敷在牙龈上的贴片）以纠正昼夜节律的改变， 睡眠和内分泌功能。 这些研究将 测试睡眠和/或昼夜节律的衰老 系统在部分负责与年龄有关的功能障碍，激素 分泌物，描绘昼夜节律/睡眠的最早改变 老化过程中发生的系统，并提供有关老化的信息 预防或纠正策略的可行性和有效性。