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: 10668411
• 负责人: Christopher Michael Depner
• 金额: $ 16.58万
• 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/10668411
• 关键词: Acceleration; Adult; Affect; American; Anxiety; Area; Award; Benchmarking; Biochemical; Biochemical Pathway; Bioinformatics; Biological; Biological Markers; Blood; Branched-Chain Amino Acids; Cardiometabolic Disease; Chronic; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Clinical assessments; Communities; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Disease; Drug abuse; Epidemic; Fingerprint; Funding; Glucose; Goals; Health; Health Benefit; Hour; Human; Individual; Inflammation; Intervention; Laboratories; Link; Mental Depression; Metabolic Diseases; Metabolic Pathway; Obesity; Outcome; Participant; Persons; Phenotype; Physiological; Plasma; Prevalence; Prevention; Proteins; Proteome; Proteomics; Protocols documentation; Public Health; Publishing; Recommendation; Research; Research Training; Risk; Sampling; Science; Sensitivity and Specificity; Sleep; Sleep Deprivation; Sleep Disorders; System; Testing; Time; Training; Translations; United States National Institutes of Health; Wakefulness; Weight Gain; Work; adequate sleep; aged; bench to bedside; biomarker identification; biomarker validation; cardiometabolic risk; cardiometabolism; circadian; clinical biomarkers; clinical diagnosis; clinical translation; cohort; diabetes risk; fatty acid metabolism; improved; insulin sensitivity; metabolome; metabolomics; novel; personalized medicine; poor sleep; primary care provider; primary outcome; programs; response; secondary outcome; shift work; timeline; week trial

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”.

项目总结/文摘