DISRUPTED SLEEP IN THE ELDERLY: CIRCADIAN ETIOLOGY

人们普遍认为，睡眠-觉醒习惯会随着年龄的增长而改变。 的 最一致的这种变化是睡眠期提前到更早 睡觉时间和早起时间。 此外，老年人往往 报告了一种“不对称”的睡眠中断，与睡眠的转变相一致。 一种潜在的节律控制着一天中较早的睡眠时间。 类似 快速眼动睡眠和体温支持的昼夜节律变化 中心假设，昼夜节律系统的相位提前到 随着年龄的增长， 在模拟的基础上，使用“双振荡器”模型的人 昼夜节律，提出了三个可检验的假设：1）， 睡眠的相位提前反映了“深”睡眠的潜在相位提前。 昼夜节律振荡器; 2）该相位在夹带条件下提前 是一个结果，年龄依赖性减少的自由运行期， 深层振荡器; 3）正常夹带刺激放大 可以逆转这种相位提前和随之而来的睡眠障碍。 一系列的实验提出了利用新的方法，允许 直接测量深振荡器的相位和周期。 这些实验 将实现四个具体目标：1）量化的年龄依赖 昼夜节律阶段的变化; 2）记录其作为 与年龄相关的睡眠障碍子集的病理生理机制; 3)阐明了改变相关系的机制， 以及; 4）评估年龄相关睡眠的潜在非药物疗法 破坏 这项工作对昼夜节律振荡器理论具有重要意义， 以及老年医学。 昼夜节律的变化 系统在病因学上与 抑郁症和疾病的病因牵连的增加， 抑郁症和体温调节障碍（体温过低）的患病率 在老年人中。 更好地理解昼夜节律机制及其 年龄依赖性改变，以及非侵入性的发展 扭转这种变化的方法，提供了实质性的承诺， 改善老年人的健康。

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.