Biomarkers and Altered Metabolic Pathways during Sleep Loss and Circadian Disruption

睡眠不足和昼夜节律紊乱期间的生物标志物和代谢途径的改变

• 批准号: 10292870
• 负责人: Christopher Michael Depner
• 金额: $ 17.44万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10292870
• 关键词: Biomarkers; Altered; Metabolic; Pathways; during

PROJECT SUMMARY/ABSTRACT Approximately 50-70 million Americans suffer from sleep and wakefulness disorders and over 35% of Americans sleep less than the recommended 7 hours per night. Additionally, ~20% of adults in the work force are shift- workers and therefore have elevated risk of circadian misalignment (i.e. sleeping during the biological day and wakefulness during the biological night). Health problems associated with insufficient sleep and circadian misalignment include inflammation, depression and anxiety, drug abuse, reduced insulin sensitivity, diabetes, and obesity. While the contribution of sleep to overall health is well recognized, many primary care providers fail to diagnose or recognize sleep and circadian disorders and estimates show undiagnosed sleep disorders are more prevalent than diagnosed sleep disorders. Currently, no clinical biomarkers of overall sleep and circadian health exist. Developing such biomarkers has the potential to: 1) improve diagnosis of sleep and circadian disorders; 2) identify biochemical mechanisms underlying increased risk of cardiometabolic disease associated with insufficient sleep and circadian misalignment; and 3) inform novel sleep and circadian based countermeasures. Long-term, biomarkers of sleep and circadian health could also support the development of personalized medicine, in part, by identifying individuals most likely to benefit from sleep and circadian based interventions. The overall goal of this K01 is to identify biomarkers of sleep loss and circadian misalignment, and assess the impact of increased sleep time on these biomarkers. I will use samples from two previously completed NIH- funded laboratory based protocols to identify putative biomarkers of insufficient sleep and circadian misalignment using plasma metabolomics and proteomics. I will also assess the plasma metabolome and insulin sensitivity in a four-week trial that increases nightly sleep duration to the recommended ≥7 hours sleep/night in habitual short-sleepers to determine if my identified biomarkers can discriminate these individuals between baseline insufficient sleep and post-increased sleep time and if increasing sleep time improves insulin sensitivity. This award will provide key training in four areas: 1) bioinformatics; 2) omics; 3) clinical translational sleep and circadian studies and interventions; and 4) professional development, and will provide essential preliminary data for an NIH R01 to help me launch an independent research program. The proposed outcomes support the 2011 NIH Sleep Disorders Research Plan to “enable sleep and circadian research training to inform science in cross-cutting domains, accelerate the pace of discovery, and the translation of enhanced therapies from bench to bedside to community”.

项目概要/摘要 大约 50-7000 万美国人患有睡眠和觉醒障碍，超过 35% 的美国人 每晚睡眠时间少于建议的 7 小时。此外，大约 20% 的成年人正在轮班—— 因此，昼夜节律失调的风险较高（即在生物日睡觉， 生物夜间的清醒状态）。与睡眠不足和昼夜节律相关的健康问题 失调包括炎症、抑郁和焦虑、药物滥用、胰岛素敏感性降低、糖尿病、 和肥胖。尽管睡眠对整体健康的贡献已得到广泛认可，但许多初级保健提供者却未能做到这一点 诊断或识别睡眠和昼夜节律紊乱，估计显示未诊断的睡眠障碍更多 比诊断出的睡眠障碍更普遍。目前，没有整体睡眠和昼夜节律健康的临床生物标志物 存在。开发此类生物标志物有潜力：1）改善睡眠和昼夜节律紊乱的诊断； 2）确定与心脏代谢疾病相关的风险增加的生化机制 睡眠不足和昼夜节律失调； 3) 提供新颖的睡眠和昼夜节律对策。 从长远来看，睡眠和昼夜节律健康的生物标志物也可以支持个性化的发展 医学部分是通过识别最有可能从睡眠和昼夜节律干预措施中受益的个体来实现的。 K01 的总体目标是识别睡眠不足和昼夜节律失调的生物标志物，并评估 睡眠时间增加对这些生物标志物的影响。我将使用来自两个先前完成的 NIH 的样本 资助基于实验室的协议，以确定睡眠不足和昼夜节律的假定生物标志物 使用血浆代谢组学和蛋白质组学进行错位。我还将评估血浆代谢组和胰岛素 一项为期 4 周的试验的敏感性，该试验将每晚睡眠时间延长至建议的 ≥7 小时睡眠/晚 习惯性短睡眠者，以确定我识别的生物标记是否可以区分这些人 基线睡眠不足和增加睡眠时间后以及增加睡眠时间是否可以改善胰岛素敏感性。 该奖项将提供四个领域的关键培训：1）生物信息学； 2）组学； 3）临床转化睡眠和 昼夜节律研究和干预措施； 4）专业发展，并将提供必要的初步 NIH R01 的数据可帮助我启动独立研究计划。拟议的成果支持 2011 年 NIH 睡眠障碍研究计划“启用睡眠和昼夜节律研究培训，为科学提供信息 交叉领域，加快发现步伐，并将增强疗法从实验室转化为 床边到社区”。