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Chapter 475: The Role of Circadian Biology in Health and Disease

Jonathan Cedernaes; Kathryn Moynihan Ramsey; Joseph Bass

INTRODUCTION

Circadian rhythms are autonomous, systemic cycles of behavior and physiology that synchronize organismal function at the cell and tissue level in anticipation of the 24-h rotation of the Earth. A common feature of modern “24/7” life is the routine disruption in these evolutionarily conserved endogenous circadian cycles, due to the rise in shift work, jet travel across time zones, exposure to blue light–emitting devices at night, and disrupted sleep. A transformation in understanding the molecular basis of circadian disorders has generated a new wave of research on metabolic disease, inflammation, aging, and cancer. This chapter provides an overview of (1) the basic biology of the circadian system; (2) primary circadian rhythm and interrelated sleep disorders; and (3) the role of the circadian system in both normal human physiology and disease states. Lastly, we review the rapidly emerging field of chronobiology as a pathway for novel diagnostic and therapeutic activity. A glossary of terms used in circadian biology is summarized in Table 475-1.

TABLE 475-1Glossary of Terms Used in Discussion of the Circadian System
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TABLE 475-1 Glossary of Terms Used in Discussion of the Circadian System
Term Description
ASPD Advanced sleep phase disorder (see text for description).
CBT Core body temperature. Often used as an indicator of the circadian rhythm, but can be masked by sleep and exercise.
CCGs Clock-controlled genes; output of the molecular clock.
Chronotype Internal circadian rhythm of an individual determined by phase of entrainment, determining sleep propensity and timing of maximum alertness over a 24-h period.
Circadian period Time required for one complete cycle or oscillation. Calculated by the time distance between two consecutive peaks or troughs of a circadian variable.
Circadian phase Timing of the circadian rhythm. Defined by comparing, e.g., the peak (acrophase) or trough (bathyphase) to a fixed event, e.g., to a point in time. Synonymous with phase angle.
Circadian rhythm A biological process that exhibits an endogenous, entrainable oscillation of approximately 24 h.
Circadian rhythm sleep disorders Disorders of multiple etiology that have in common that they result in maladjustment of the biological clock with respect to the environment.
Constant routine An experimental paradigm designed to study endogenous circadian rhythms in humans, by keeping behavioral and environmental factors constant. These paradigms thereby entail constant dim lighting, evenly distributed isocaloric energy intake, semi-recumbent posture, and forced wakefulness.
Desynchrony Loss of synchrony occurring either between a rhythm and its Zeitgeber (external), or between two or more rhythms within an organism (internal).
Diurnal rhythm An oscillation synchronized with the day/night cycle that repeats itself with a 24-h period. The rhythm does not have to persist when time cues (e.g., light) are absent.
DLMO Dim-light melatonin onset; a marker of melatonin rhythm.
DSPD Delayed sleep phase disorder (see text for description).
Entrainment Synchronization of a circadian rhythm or other self-sustaining oscillation by a factor—Zeitgeber—that enforces the oscillator. Constant entrainment between the Zeitgeber and the ...

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