Biomarkers for Peripheral Circadian Clocks in Humans

人类外周生物钟的生物标志物

• 批准号: 10687428
• 负责人: Kenneth P Wright
• 金额: $ 77.95万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10687428
• 关键词: Address; Adipose tissue; Behavior; Behavioral; Biological Markers; Body Temperature; C-reactive protein; Cells; Circadian Rhythms; Circadian desynchrony; Clinical Trials; Cues; Data; Development; Disease; Eating; Endothelial Cells; Endothelium; Food; Future; Gene Expression; Glucocorticoids; Glucose; Goals; Health; Hormones; Human; Hydrocortisone; Hypothalamic structure; Immune; Isomerism; Knowledge; Lead; Leptin; Ligands; Light; Liver; Melatonin; Metabolic; Methodology; Outcome; Parathyroid gland; Peptide YY; Periodicity; Peripheral; Phase; Physical activity; Physiological; Physiological Processes; Plasma Proteins; Plasminogen Activator Inhibitor 1; Precision Medicine Initiative; Process; Proteins; Proteome; Proteomics; Protocols documentation; Publishing; Randomized; Regulation; Research; Sampling; Sleep Disorders; Small Intestines; Stomach; Strategic Planning; Structure; Sympathetic Nervous System; Testing; Theoretical model; Time; Tissues; United States National Institutes of Health; analytical tool; base; biomarker development; bone; chemokine; circadian; circadian pacemaker; fundamental research; ghrelin; improved; in vivo; men; novel; novel marker; response; suprachiasmatic nucleus; treatment strategy

PROJECT SUMMARY/ABSTRACT Circadian clocks are present in most tissues of the body with importance for optimal physiological function and behavior. Misalignment or disruption of peripheral circadian clocks contribute to disease and thus represent promising novel treatment targets to improve health. The overall goal of this proposal is to improve our understanding of peripheral circadian clocks in humans. We will conduct a seven-weeklong randomized, crossover, mechanistic clinical trial to 1) test zeitgebers (time cues) for already identified markers of peripheral clocks, and 2) identify novel biomarkers for peripheral clocks and explore zeitgebers for those clocks in humans. Preliminary data from our human circadian basic and clinical trial research set the stage for this proposal. This mechanistic clinical trial effort is a first step to inform future development of novel circadian based treatments for aligning peripheral clocks and for developing novel circadian biomarkers that will advance our scientific understanding of circadian rhythms. Our overall goal and aims support the NIH Precision Medicine Initiative and the NIH Sleep Disorders Research Strategic Plan.

项目概要/摘要 生物钟存在于身体的大多数组织中，对于最佳的生理功能和 行为。外周生物钟的失调或破坏会导致疾病，因此代表 有前景的改善健康的新治疗目标。该提案的总体目标是改善我们的 了解人类的外周生物钟。我们将进行为期七周的随机、 交叉、机械临床试验 1) 测试 zeitgebers（时间线索）是否已识别的外周标记物 时钟，2) 识别外周时钟的新型生物标志物，并探索人类这些时钟的时间。 我们的人类昼夜节律基础和临床试验研究的初步数据为该提案奠定了基础。这 机械临床试验工作是为未来开发基于昼夜节律的新型治疗方法提供信息的第一步 调整外围时钟并开发新颖的昼夜节律生物标志物，这将推进我们的科学 了解昼夜节律。我们的总体目标和目的支持 NIH 精准医学计划和 美国国立卫生研究院睡眠障碍研究战略计划。