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 对人类外周生物钟的理解。我们将进行为期七周的随机、 交叉、机械性临床试验：1)测试已确定的外周疾病标志物的时间线索 2)识别外周生物钟的新生物标志物，并探索人类体内这些生物钟的计时器。 来自我们的人体昼夜节律基础和临床试验研究的初步数据为这一提议奠定了基础。这 机械性临床试验努力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 调整外围时钟和开发新的昼夜节律生物标志物，将推动我们的科学 理解昼夜节律。我们的总体目标和宗旨是支持NIH精密医学倡议和 美国国立卫生研究院睡眠障碍研究战略计划。

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 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.