Biomarkers for Peripheral Circadian Clocks in Humans

Overview

The purpose of this project is to improve our understanding of peripheral circadian rhythms in humans. Circadian clocks are present in most tissues of the body with importance for optimal physiological function, health, and behavior. This project will utilize simulated jetlag protocols to systematically test novel hypotheses about the regulation of peripheral circadian rhythms in humans. Specifically, we will examine how changes in the time of when we are exposed to light and the timing of when we eat impacts proteins in the blood and saliva that represent rhythms from clocks in the brain (e.g., rhythms of the hormones melatonin and cortisol coordinated by the brain) and rhythms from clocks in body tissues (e.g., proteins made by immune and bone cells, and cells in the stomach and liver). We also aim to discover new blood-based biomarkers of peripheral rhythms in humans. We anticipate our findings will be the first step in developing novel circadian based treatments for aligning peripheral clocks under conditions such as jetlag, and for developing novel circadian biomarkers that will advance our scientific understanding of circadian rhythms.

Visit 1: Participants who meet pre-screen/initial inclusion criteria will be consented at Visit 1, complete additional questionnaires and interviews to assess inclusion/exclusion criteria, and we will collect descriptive data as well as have our clinical psychologist perform a clinical interview. Visit 2: Participants will undergo medical screening at the Clinical Translational Research Center at the University of Colorado Boulder (UCB-CTRC) to determine health status. Visits 3 \& 6: Participants will be asked to maintain a regular \~8h sleep-wake schedule for two weeks prior to Visits 5 and 8. Participants will wear a wrist activity, skin temperature, and light exposure recorder. Participants will be asked to remain in the local time zone during ambulatory recording procedures and be asked to keep their typical schedules (e.g., not stay up all night for work or social events and not reside in a new place different from their place of residence). Visit 4 \& 7: Participants will come to the laboratory on days 11 and 39, where qualified staff will apply a Continuous Glucose Monitoring (CGM) sensor to be worn for \~3 days at home and will continue in the laboratory. For the three days leading up to the study isocaloric meals including breakfast, lunch, and dinner will be provided. Participants will be asked to consume these energy balanced research diets (no caffeine) and meal timing will be scheduled (breakfast \~30 min, lunch \~5h, and dinner \~10h after awakening,). Exercise will be proscribed for these 3-days prior to the in-lab study. Visits 5 \& 8: Participants will be randomized to condition order using an ABBA design (i.e., randomized into one of the two experimental conditions first in a crossover design: 3-days bright light exposure or 3-days of earlier timed meals). Both conditions are tested under an advanced sleep-wake schedule equivalent to traveling 5 time zones east. All participants will complete both conditions. On the second visit, participants will be tested in the other condition. Participants will live in the laboratory for 7.7 days each visit.