Alerations of Sleep and Circadian Timing in Aging

描述（由申请人提供）：我们的团队已经确定睡眠时间减少是肥胖和2型糖尿病的一个新的危险因素。在之前的资助期间，我们已经证明睡眠质量下降，特别是深度慢波睡眠（SWS）减少，具有不利的心脏代谢后果，并获得了“恶性循环”可能将睡眠和昼夜节律中断与心脏代谢疾病联系起来的证据。在人类和啮齿类动物中，我们进一步观察到，慢性部分睡眠限制会改变睡眠的稳态调节，这种现象可能被称为睡眠调节的“异稳态”。正常的衰老与睡眠时间、睡眠质量和昼夜节律功能的减少有关。目前的项目重点关注睡眠时间、睡眠质量和昼夜节律功能的慢性减少与年龄相关的心脏代谢疾病增加之间的相互作用。将采用多学科方法，结合大数据集的统计分析、临床研究（所有年龄的健康成年人、老年失眠症患者和有睡眠障碍的老年人）、慢性部分睡眠缺失啮齿动物模型的体内研究以及分子和遗传分析：1。验证由于年龄、种族或遗传因素导致的低SWS个体患2型糖尿病的风险更高的假设（人类研究，E. Van Cauter， PI）；2. 验证SWS的保存或恢复具有有益心脏代谢作用的假设（人类研究，E. Tasali， PI）；3. 验证老年人最常见的失眠类型与SWS降低和心脏代谢改变有关的假设（人类研究；P.C. Zee， PI）；4. 对慢性部分睡眠限制期间年龄对睡眠不平衡的影响进行综合评估，并确定心脏代谢后果（大鼠研究；F.W. Turek， PI）；5. 剖析由昼夜节律紊乱和睡眠缺失引起的加速代谢衰老的分子基础（小鼠研究；J. Bass， PI）。核心A（行政）将提供后勤和财务协调。核心B（方法和分析）将规范数据收集、存档和分析的操作程序。Core C将检测外周激素、细胞因子和其他血液成分的水平。

DESCRIPTION (provided by applicant): Our group has identified reduced sleep duration as a novel risk factor for obesity and type 2 diabetes. During the previous grant period, we have shown that reduced sleep quality, specifically reduced deep slow-wave sleep (SWS), has adverse cardiometabolic consequences and obtained evidence that a "vicious cycle" may interconnect sleep and circadian disruption with cardiometabolic disease. In both humans and rodents, we further observed that chronic partial sleep restriction alters the homeostatic regulation of sleep, a phenomenon that may be referred to as an "allostasis" of sleep regulation. Normal aging is associated with reductions in sleep duration, sleep quality and circadian function. The present Program Project focuses on the interactions between chronic reductions of sleep duration, sleep quality and circadian function and the age-related increase in cardiometabolic disease. A multi-disciplinary approach combining statistical analyses of a large data set, clinical research (in healthy adults of all ages, older insomniacs, and older adults with sleep disturbances), in vivo studies in a rodent model of chronic partial sleep loss and molecular and genetic analyses will be used to: 1. test the hypothesis that individuals with low SWS because of age, ethnicity or genetic factors, are at higher risk for type 2 diabetes (human studies, E. Van Cauter, PI); 2. test the hypothesis that the preservation or restoration of SWS has beneficial cardiometabolic effects (human studies, E. Tasali, PI); 3. test the hypothesis that the most common types of insomnia in older adults are associated with reduced SWS and cardiometabolic alterations (human studies; P.C. Zee, PI); 4. perform a comprehensive evaluation of the impact of age on sleep allostasis during chronic partial sleep restriction and determine the cardiometabolic consequences (rat studies; F.W. Turek, PI); 5. dissect the molecular basis for accelerated metabolic aging induced by circadian disruption and sleep loss (mouse studies; J. Bass, PI). Core A (Administrative) will provide logistic and financial coordination. Core B (Methods and Analysis) will standard operating procedures for data collection, archival and analysis. Core C will assay peripheral levels of hormones, cytokines and other blood constituents.