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Circadian Rhythm Phase Shifts Caused by Timed Exercise Vary with Chronotype in Young Adults University of Kentucky UKnowledge Theses and Dissertations--Kinesiology and Health Promotion Kinesiology and Health Promotion 2019 CIRCADIAN RHYTHM PHASE SHIFTS CAUSED BY TIMED EXERCISE VARY WITH CHRONOTYPE IN YOUNG ADULTS J. Matthew Thomas University of Kentucky, [email protected] Digital Object Identifier: https://doi.org/10.13023/etd.2019.406 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Thomas, J. Matthew, "CIRCADIAN RHYTHM PHASE SHIFTS CAUSED BY TIMED EXERCISE VARY WITH CHRONOTYPE IN YOUNG ADULTS" (2019). Theses and Dissertations--Kinesiology and Health Promotion. 64. https://uknowledge.uky.edu/khp_etds/64 This Doctoral Dissertation is brought to you for free and open access by the Kinesiology and Health Promotion at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Kinesiology and Health Promotion by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless an embargo applies. I retain all other ownership rights to the copyright of my work. I also retain the right to use in future works (such as articles or books) all or part of my work. I understand that I am free to register the copyright to my work. REVIEW, APPROVAL AND ACCEPTANCE The document mentioned above has been reviewed and accepted by the student’s advisor, on behalf of the advisory committee, and by the Director of Graduate Studies (DGS), on behalf of the program; we verify that this is the final, approved version of the student’s thesis including all changes required by the advisory committee. The undersigned agree to abide by the statements above. J. Matthew Thomas, Student Dr. Jody L. Clasey, Major Professor Dr. Melinda Ickes, Director of Graduate Studies CIRCADIAN RHYTHM PHASE SHIFTS CAUSED BY TIMED EXERCISE VARY WITH CHRONOTYPE IN YOUNG ADULTS ________________________________________ DISSERTATION ________________________________________ A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Education at the University of Kentucky By J. Matthew Thomas Lexington, Kentucky Director: Dr. Jody L. Clasey, Professor of Kinesiology and Health Promotion Lexington, Kentucky 2019 Copyright © J. Matthew Thomas 2019 ABSTRACT OF DISSERTATION CIRCADIAN RHYTHM PHASE SHIFTS CAUSED BY TIMED EXERCISE VARY WITH CHRONOTYPE IN YOUNG ADULTS The circadian system controls 24-hour cycles of behavior and physiology, such as rest- activity and feeding rhythms. The human circadian system synchronizes with, or entrains to, the light/dark cycle (sunrise/sunset) to promote activity and food consumption during the day and rest at night. However, strict work schedules and nighttime light exposure impair proper entrainment of the circadian system, resulting in chronic circadian misalignment. Numerous studies have shown that chronic circadian misalignment results in poor health. Therefore, therapeutic interventions that could shift circadian rhythms and alleviate circadian misalignment could broadly impact public health. Although light is the most salient time cue for the circadian system, several laboratory studies have shown that exercise can also entrain the internal circadian rhythm. However, these studies were performed in controlled laboratory conditions with physically-active participants. The purpose of this study was to determine whether timed exercise can phase advance (shift earlier) the internal circadian rhythm in sedentary subjects in free-living conditions. Fifty- two young, sedentary adults (16 male, 24.3±0.76 yrs) participated in the study. As a marker of the phase of the internal circadian rhythm, we measured salivary melatonin levels (dim light melatonin onset: DLMO) before and after 5 days of timed exercise. Participants were randomized to perform either morning (10h after DLMO) or evening (20h after DLMO) supervised exercise training for 5 consecutive days. We found that morning exercisers had a significantly greater phase advance than evening exercisers. Importantly, the morning exercisers had a 0.6h phase advance, which could theoretically better align their internal circadian rhythms with the light-dark cycle and with early- morning social obligations. In addition, we also found that baseline DLMO, a proxy for chronotype, influenced the effect of timed exercise. We found that for later chronotypes, both morning and evening exercise advanced the internal circadian rhythm. In contrast, earlier chronotypes had phase advances when they exercised in the morning, but phase delays when they exercised in the evening. Thus, late chronotypes, who experience the most severe circadian misalignment, may benefit from exercise in the morning or evening, but evening exercise may exacerbate circadian misalignment in early chronotypes. Together these results suggest that personalized exercise timing prescriptions based on chronotype could alleviate circadian misalignment in young adults. KEYWORDS: Circadian Rhythms, Chronotype, Circadian Misalignment Exercise, Phase Shift J. Matthew Thomas October 11, 2019 Date CIRCADIAN RHYTHM PHASE SHIFTS CAUSED BY TIMED EXERCISE VARY WITH CHRONOTYPE IN YOUNG ADULTS By J. Matthew Thomas Dr. Jody L. Clasey Director of Dissertation Dr. Melinda Ickes Director of Graduate Studies September 16, 2019 Date Table of Contents List of Tables……………….………..……………………………………..…….………vi List of Figures…………...………………………………..…………………………..….vii Chapter 1: Review of Literature……………………………….………..…………1 1.1 Overview…………………………………………………………….……1 1.2 Circadian rhythms in humans…….………………………..………...……2 1.2.1 What is a circadian rhythm?……..………………………………….2 1.2.2 Fundamental properties………..……………………………….……2 1.2.3 How are circadian rhythms generated?…………...….………….…..4 1.2.3.1 Circadian pacemaker……………...………………..………..4 1.2.3.2 Molecular mechanism…..……………….…..……...……..…5 1.2.3.3 Peripheral circadian oscillators in mammals……..…..…..….7 1.2.4 Modulation of circadian rhythms…………….…….…………….....9 1.2.5 Measuring human circadian rhythms……….…………………..…12 1.2.5.1 Melatonin………….…..…..……………………....……….12 1.2.5.2 Body temperature…………....………………………..…...14 1.2.5.3 Actigraphy…….……...…….……………………….……..15 1.2.5.4 Subjective questionnaires………...………....………….….16 1.2.6 Disruption of human circadian rhythms……………………..…….17 1.2.6.1 Shift work……………..……………………….…………..17 1.2.6.2 Circadian misalignment………....……………..………….18 1.2.6.2.1 Chronotype………………..……………….……19 1.2.6.2.2 Impact of chronotype on human performance and health…………………………………………...….……...21 1.2.6.2.3 Social jetlag…….……………..……….………..23 1.2.6.2.4 Other measures of circadian misalignment…..…24 1.2.7 Interventions targeting the circadian system……………………..26 1.2.7.1 Light therapy…………..…..………….…………….……26 iii 1.2.7.2 Time restricted feeding…………..………………….…...26 1.2.7.3 Melatonin………………………..…..………….………..28 1.2.7.4 Physical activity……………..…………..…………..…...28 1.3 Physical activity and human health……………………………………….29 1.3.1 Importance of physical activity and physical fitness…….……..…..29 1.3.2 Physical activity dose-response……...….…….…..………………..30 1.3.3 Physical activity and sleep……………...………….……………….33 1.3.4 Measurement of physical fitness ……………….…….……………34 1.3.4.1 Cardiorespiratory fitness……..…..………………………..34 1.3.4.2 Body composition……..…….…………………………….35 1.3.4.3 Muscular Fitness………....…………………………..……36 1.3.4.4 Flexibility……………..…………………………..……….36 1.3.5 Measurement of physical activity………....………………..………36 1.3.5.1 Accelerometers………..…..……...……………………….36 1.4 Physical activity and circadian rhythms…………………….……………..37 1.4.1 Phase shifting the circadian clock with exercise……..………....….37 1.4.2 Mechanisms causing exercise phase shifts…….…….…….…...…..44 1.4.3 Exercise timing and performance……………....……………….….44 1.5 Conclusion…………………………………………………….……………46 Chapter 2: Circadian rhythm phase shifts caused by timed exercise vary with chronotype in young adults…………………….…………….…………..……………...47 2.1 Abstract……………………………………………………………………..47 2.2 Introduction…………………..……………………………………………..49 2.3 Results……………………………………………………………………....50 2.3.1 Study Participants…………………………………………………….50 2.3.2 The time of exercise affects the phase of circadian rhythms in young, sedentary adults………………………………………..………….....51 2.3.3 Chronotype is associated with phase shifts in evening exercisers.......55 2.4 Discussion…………………………………………………………………..57 iv 2.5 Methods……………………………………………………………………..61 2.5.1 Participants……………………………………………………………61 2.5.2 Study protocol…………………………………………………………61 2.5.3 Chronotype questionnaires……...……………………………………..62 2.5.4 Anthropometric and body composition measures…….……..………...62 2.5.5 Actigraphy……………………………...…………………………...…63 2.5.6 Circadian phase measure:
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