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.