DISRUPTED SLEEP IN THE ELDERLY: CIRCADIAN ETIOLOGY

人们普遍认为，睡眠-醒来的习惯会随着年龄的增长而改变。这个 最一致的这种变化是睡眠时间提前到更早 就寝时间和早起时间。此外，年长的人往往 报告睡眠“不对称”中断，与睡眠时间的变化相一致 将睡眠控制在一天中较早时间的潜在节律。类似 快速眼动睡眠和体温支持的昼夜节律变化 昼夜节律系统的阶段推进到 年龄越大，时间越早。 基于对人体“双振子”模型的模拟 关于昼夜节律，提出了三个可检验的假设：1) 睡眠的阶段推进反映了“深层”的潜在阶段推进。 昼夜节律振荡器；2)该相位在夹带条件下推进 是自由运行期随年龄增长而减少的结果 深层振荡器；以及3)正常诱导性刺激放大 可以逆转这一阶段的推进和随之而来的睡眠障碍。 建议利用新的方法进行一系列实验，以使 深度振荡器相位和周期的直接测量。这些实验 将实现四个具体目标：1)量化与年龄相关的 昼夜节律阶段的变化；2)记录其作为 一组年龄相关睡眠障碍的病理生理机制； 3)阐明改变相关系的机制， 以及4)对年龄相关性睡眠的潜在非药物疗法的评估 颠覆。 这项工作对昼夜节律振荡器理论具有重要意义 老年医学也是如此。昼夜节律的年龄相关变化 系统在病因学上与增加的发病率有关 抑郁症和精神障碍的病因牵连增加 抑郁和体温调节障碍的患病率(体温过低) 在老年人中。更好地理解昼夜节律机制及其 年龄依赖性的改变以及非侵袭性的发展 扭转这一变化的方法，为 改善老年人的健康状况。

It is generally appreciated that sleep-wake habits change with age. The most consistent such change is the advance of the sleep period to earlier bedtimes and earlier arising times. In addition, older individuals often report an "assymmetric" disruption of sleep, consistent with a shift of the underlying rhythm controlling sleep to an earlier time of day. Similar changes in the circadian rhythms of REM sleep and body temperature support the central hypothesis that the phase of the circadian system advances to an earlier time with increased age. On the basis of simulations using the "dual-oscillator" model of human circadian rhythms, three testable hypotheses are proposed: 1) that the phase advance of sleep reflects an underlying phase advance of the "deep" circadian oscillator; 2) that this phase advance under entrained conditions is a consequence of an age-dependent decrease in the free-running period of the deep oscillator; and 3) that amplification of normal entraining stimuli can reverse this phase advance and the consequent sleep disturbance. A series of experiments are proposed utilizing new methodologies that allow direct measurement of deep oscillator phase and period. These experiments will accomplish four specific aims: 1) quantification of an age-dependent change in circadian phase; 2) documentation of its role as the pathophysiologic mechanism in a subset of age-related sleep disturbances; 3) elucidation of the mechanism underlying the altered phase relations, and; 4) evaluation of a potential non-drug therapy for age-related sleep disruption. This work has significant implications for circadian oscillator theory as well as for gerontologic medicine. Age-related changes in the circadian system have been etiologically implicated in the increased prevalence of depression and disorders of etiologically implicated in the increased prevalence of depression and disorders of thermoregulation (hypothermia) among the aged. Greater understanding of circadian mechanisms and their age-dependent alteration, as well as the development of non-invasive methods for reversing this alteration, offer substantive promise for improved health of the elderly.