Alerations of Sleep and Circadian Timing in Aging

衰老过程中睡眠和昼夜节律的变化

基本信息

批准号：
8245081
负责人：
Eve Van Cauter
金额：
$ 189.68万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-02-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8245081
关键词：
Accounting Address Adult Adverse effects Advisory Committees Affect Age Aging Aging-Related Process Agreement American Animal Experimentation Animal Model Animals Anthropology Appetite Regulation Area Attention Award Basic Science Bass Beds Behavior Behavioral Beta Cell Biochemical Pathway Biochemistry Biological Biological Assay Biological Preservation Biological Sciences Biology Blood Blood Volume Body Weight Brain Calories Capital Cardiology Cardiovascular Diseases Cardiovascular system Cell physiology Chicago Chronic Chronic Insomnia Chronobiology Circadian Dysregulation Circadian Rhythms Clinical Clinical Research Clinical Trials Cognition Coin Collaborations Commit Communities Continuous Positive Airway Pressure Country DSM-IV Data Data Analyses Data Collection Data Set Development Diabetes Mellitus Diagnosis Diet Digestive System Disorders Discipline Discipline of Nursing Disease Doctor of Medicine Doctor of Philosophy Education Educational Activities Educational workshop Elderly Elevator Endocrine Endocrinology Energy Intake Energy Metabolism Ensure Environment Epidemic Epidemiologic Studies Equipment Ethnic Origin Explosion Facilities and Administrative Costs Failure Family member Fatigue Fatty acid glycerol esters Fertilization Financial compensation Floor Food Foundations Functional disorder Funding Future Gender Gene Expression Genes Genetic Genetic Predisposition to Disease Genetic Transcription Gerontology Glucose tolerance test Goals Gold Gonadal Steroid Hormones Grant Health Heritability High Prevalence Hispanics Hormonal Hormones Hospitals Hour Housing Human Hunger Impact evaluation Impairment In Vitro Individual Individual Differences Inflammation Institutes Institution Insulin-Dependent Diabetes Mellitus Intake Interest Group Internal Medicine Intervention Joints K-Series Research Career Programs Kidney Diseases Knowledge Label Laboratories Laboratory Research Laboratory Study Lead Learning Length Leptin Life Link Location Logistics Longitudinal Studies Measures Mediating Medical Research Medical center Medicine Mental Depression Metabolic Metabolic Pathway Metabolic syndrome Metabolism Methods Mission Molecular Molecular Genetics Molecular Models Molecular and Cellular Biology Multicenter Studies Mus Mutant Strains Mice Mutation National Heart, Lung, and Blood Institute National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases Nature Neuraxis Neuroanatomy Neurobiology Neurocognitive Deficit Neuroendocrinology Neurology Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Obstructive Sleep Apnea Organ Outcome Overweight Participant Pathway interactions Patient Self-Report Patients Performance Periodicity Peripheral Pharmacologic Substance Phase Phenotype Physical activity Physicians Physiological Physiology Play Postdoctoral Fellow Predisposition Pregnancy Premature Birth Principal Investigator Procedures Psychology Pulmonology Quality of life Race Rattus Recovery Recurrence Regulation Reporting Reproductive Biology Request for Applications Research Research Activity Research Personnel Research Project Grants Research Subjects Research Training Resources Rest Risk Risk Factors Rodent Rodent Model Role Satiation Scientist Services Severities Side Sleep Sleep Apnea Syndromes Sleep Deprivation Sleep Disorders Sleep Fragmentations Sleep Wake Cycle Sleep disturbances Sleeplessness Slow-Wave Sleep Social Work Socioeconomic Status Specialist Staging Stress Sum Supervision System TNFRSF5 gene Teaching Hospitals Technology Testing Tetracyclines Ticks Time Tissues Training Translating Translational Research Travel Twin Studies United States National Center for Health Statistics United States National Institutes of Health Universities Wages Wakefulness Water Weight Weight Gain Woman Work Writing age related allostasis allostatic load animal care animal resource authority base biological adaptation to stress blood glucose regulation circadian pacemaker cohort community health study cooking cost cytokine db/db mouse depressive symptoms design diabetes risk experience feeding fly gene discovery gene function genetic analysis genetic pedigree ghrelin glucose metabolism high risk impaired glucose tolerance improved in vivo insight insulin secretion insulin sensitivity interdisciplinary approach interest islet amyloid polypeptide leptin receptor medical schools member middle age molecular modeling mouse model mutant neurobehavioral normal aging novel novel strategies nutrition obesity risk patient population pre-doctoral premature professor programs prospective research study residence response restoration sedentary sex sleep regulation square foot success tool trait treatment duration young adult

项目摘要

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.

描述（由申请人提供）：我们的小组已确定睡眠时间缩短是肥胖和 2 型糖尿病的新危险因素。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）的减少，会对心脏代谢产生不良后果，并获得证据表明“恶性循环”可能将睡眠和昼夜节律破坏与心脏代谢疾病联系起来。在人类和啮齿类动物中，我们进一步观察到，慢性部分睡眠限制改变了睡眠的稳态调节，这种现象可称为睡眠调节的“动态平衡”。正常衰老与睡眠时间、睡眠质量和昼夜节律功能的减少有关。本项目重点关注睡眠时间、睡眠质量和昼夜节律功能的长期减少与年龄相关的心脏代谢疾病增加之间的相互作用。一种多学科方法，结合大数据集的统计分析、临床研究（在所有年龄段的健康成年人、老年失眠症患者和患有睡眠障碍的老年人中）、慢性部分睡眠缺失的啮齿动物模型的体内研究以及分子和遗传分析将用于： 1. 检验以下假设：由于年龄、种族或遗传因素而导致 SWS 较低的个体患 2 型糖尿病的风险较高（人类研究，E. Van Cauter，PI）； 2. 检验保存或恢复 SWS 具有有益心脏代谢作用的假设（人类研究，E. Tasali，PI）； 3. 检验老年人最常见的失眠类型与 SWS 减少和心脏代谢改变相关的假设（人体研究；P.C. Zee，PI）； 4. 对慢性部分睡眠限制期间年龄对睡眠失衡的影响进行全面评估，并确定心脏代谢后果（大鼠研究；F.W. Turek，PI）； 5. 剖析昼夜节律紊乱和睡眠不足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）将制定数据收集、归档和分析的标准操作程序。 Core C 将检测激素、细胞因子和其他血液成分的外周水平。