Sleep, Aging and Circadian Rhythm Disorders

描述（由申请人提供）：老年人的睡眠特点是难以启动，频繁觉醒和早醒。虽然对老年人急性睡眠剥夺的后果进行了调查，但对许多老年人所经历的慢性睡眠不足的后果知之甚少。此外，还没有研究过老年人中常见的昼夜节律相位失调与慢性睡眠不足之间的相互作用。我们的建议试图通过使用一个完善的实验室模型来研究在长期睡眠限制的条件下老年人和年轻人的睡眠效率之间可能存在的差异来解决我们知识中的这一差距（比率19小时预定唤醒：5小时的预定睡眠），在强迫睡眠协议上进行，以及通过评估在这种限制之后的睡眠延长条件下的恢复能力。我们的人类受试者协议的设计提供了一个巨大的机会，调查这些条件下的慢性睡眠限制和随后的睡眠延长的认知性能的措施。拟议计划项目的多导睡眠描记核心将为参与实验方案的受试者以及筛选过程中的潜在受试者的多导睡眠描记记录提供准确可靠的评分。我们的建议中包括了一个“代谢老化”实验，目的是了解睡眠限制对年轻人和老年人的内分泌和心血管影响。在本项目的上一个周期中，有人假设老年人的睡眠困难可能是由于腹外侧视前核（VLPO）神经元的丢失。这一提议的一个关键组成部分是继续追求这种哺乳动物模型在衰老过程中的睡眠调节。随着年龄的增长，腹外侧视前核（VLPO）中的神经元会丢失，而这是正常睡眠所必需的，随着年龄的增长，我们假设VLPO部分病变的大鼠是老年人睡眠的高保真模型。我们将通过在老年大鼠和部分VLPO病变的大鼠中进行一系列与本计划项目资助的人类部分平行的研究来测试该模型对老年人的有效性。我们假设VLPO损伤的大鼠是VLPO细胞丢失的老年人睡眠的良好模型，并使用该模型来测试旨在恢复VLPO功能的治疗的有效性，我们希望这将恢复睡眠以及改善认知和运动技能随着衰老和睡眠不足而恶化。核心组件-管理，分析和多导睡眠图-在跨项目提供支持方面是有效的，最重要的是，在整个计划项目中提供工作的凝聚力。这项研究的结果将对了解睡眠在老年人健康，安全和神经认知功能中的作用具有重要意义。

DESCRIPTION (provided by applicant): Sleep in older people is marked by difficulty with initiation, frequent arousals, and early awakening. While the consequences of acute sleep deprivation have been investigated in older people, very little is known about the consequences of the chronic insufficient sleep experienced by many older people. Moreover, the interaction between the misalignment of circadian phase, so common in older people, and chronic insufficient sleep has not been studied. Our proposal seeks to address that gap in our knowledge by using a well-established laboratory model to study what differences may exist between the sleep efficiency of older and younger subjects under conditions of chronic sleep restriction (ratio 19 hours scheduled wake: 5 hours scheduled sleep), carried out on a forced-desynchrony protocol, and by assessing the recuperative capabilities under conditions of sleep extension following this restriction. The design of our human subjects protocol provides a tremendous opportunity to investigate an array of cognitive performance measures under these conditions of chronic sleep restriction and subsequent sleep extension. The Polysomnography Core of the proposed Program Project will provide accurate and reliable scoring of polysomnographic recordings from subjects participating in the experimental protocol as well as from prospective subjects during the screening process. A 'metabolic aging' experiment has been included in our proposal with the goal of understanding the endocrine and cardiovascular consequences of sleep restriction in both young and older subjects. In the previous cycle of this Program Project, it was hypothesized that sleep difficulties in older people might be due to loss of neurons in the ventrolateral preoptic nucleus (VLPO). A critical component of this proposal is the continued pursuit of this mammalian model for sleep regulation during aging. With aging, there is a loss of neurons in the ventrolateral preoptic nucleus (VLPO), which is necessary for normal sleep, with aging, and we hypothesize that rats with partial lesions of the VLPO are a high fidelity model for sleep in older people. We will test this model for its validity for older people by performing a series of studies that parallel the human components of this Program Project grant, both in older rats and in rats with partial VLPO lesions. We hypothesize that the VLPO lesioned rat is a good model for sleep in older people who have VLPO cell loss, and to use this model to test the efficacy of treatment designed to restore VLPO function, which we hope will restore sleep as well as improve cognitive and motor skills that deteriorate with aging and poor sleep. The core components - Administrative, Analytic and Polysomnography - are effective in providing support across projects and most importantly, providing for cohesion of efforts across the entire Program Project. The results of this research will have important implications for understanding the role of sleep in the health, safety, and neurocognitive functions of older people.