Biomarkers for Peripheral Circadian Clocks in Humans

项目总结/摘要 昼夜节律钟存在于身体的大多数组织中，对于最佳生理功能具有重要性， 行为外周生物钟的失调或破坏会导致疾病，因此代表 有望成为改善健康的新治疗靶点。该提案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，机械临床试验，以1）测试已经确定的外周血淋巴细胞标志物的时间标记（时间线索） 生物钟，以及2）识别外周生物钟的新生物标志物，并探索人类中这些生物钟的时间表。 我们的人类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 机械临床试验工作是告知未来开发基于昼夜节律的新治疗方法的第一步。 调整外周生物钟，开发新的昼夜节律生物标志物， 对昼夜节律的理解。我们的总体目标和宗旨支持NIH精准医学计划， NIH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.