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J Appl Physiol 92: 852-862, 2002; doi:10.1152/japplphysiol.00924.2001
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Vol. 92, Issue 2, 852-862, February 2002

HIGHLIGHTED TOPICS
Functional Genomics of Sleep and Circadian Rhythm
Invited Review: Integration of human sleep-wake regulation and circadian rhythmicity

Derk-Jan Dijk1 and Steven W. Lockley2

1 Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford GU27XH, United Kingdom; and 2 Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

sleep homeostasis; entrainment; clock genes; blindness; aging


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