Biomarkers for Peripheral Circadian Clocks in Humans

项目摘要/摘要 生物钟存在于身体的大多数组织中，对最佳的生理功能和 行为。外周生物钟的错位或扰乱会导致疾病，因此代表 有希望的新的治疗目标，以改善健康。这项建议的总体目标是改善我们的 对人类外周昼夜节律的理解。我们将进行为期七周的 随机、交叉、机械性临床试验：1)测试外周昼夜节律的时间线索 节律，以及2)识别外周节律的新生物标记物，并探索这些节律的分子标记 人类。来自人类昼夜节律基础和临床试验研究的初步数据为此奠定了基础 求婚。这一机械性的临床试验工作是为未来发展新的昼夜节律提供信息的第一步。 用于调整外周时钟和开发新的昼夜生物标志物的基于治疗的方法 推进我们对昼夜节律的科学理解。我们的总体目标和宗旨是支持NIH 精准医学倡议和NIH睡眠研究战略计划。

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 rhythms in humans. We will conduct a seven-weeklong randomized, crossover, mechanistic clinical trial to 1) test zeitgebers (time cues) for peripheral circadian rhythms, and 2) identify novel biomarkers for peripheral rhythms and explore zeitgebers for those rhythm 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 Research Strategic Plan.