Nearly all physiological and behavioral functions in humans occur on a rhythmic basis, which in turn leads to dramatic diurnal rhythms in human performance capabilities. Regardless of whether it results from voluntary (e.g., shift work or rapid travel across time zones) or involuntary (e.g., illness or advanced age) circumstances, a disturbed circadian rhythmicity in humans has been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity.
Many adverse effects of disrupted circadian rhythmicity may, in fact, be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.
For most animals, the timing of sleep and wakefulness under natural conditions is in synchrony with the circadian control of the sleep cycle and all other circadian-controlled rhythms. Humans, however, have the unique ability to cognitively override their internal biological clock and its rhythmic outputs. When the sleep-wake cycle is out of phase with the rhythms that are con-trolled by the circadian clock (e.g., during shift work or rapid travel across time zones), adverse effects may ensue.
In addition to the sleep disturbances associated with jet lag or shift work, sleep disorders can occur for many other known and unknown reasons. And although disturbed sleep is a hallmark of many human mental and physiological disorders, notably affective disorders, it is often unclear whether the sleep disturbances contribute to or result from the illness. Other circadian rhythm abnormalities also are often associated with various disease states, although again the importance of these rhythm abnormalities in the development (i.e., etiology) of the disease remains unknown (Brunello et al. 2000).
One important factor contributing to researchers’ inability to precisely define the role of circadian abnormalities in various disease states may be the lack of knowledge of how circadian signals from the SCN are relayed to target tissues. To further elucidate the regulation of circadian rhythms, researchers need a better understanding of the nature of circadian signal output from the SCN and of how these output signals may be modified once they reach their target systems. Such an enhanced understanding also would allow for a better delineation of the importance of normal temporal organization for human health and disease.
The finding that two major causes of death-heart attacks and strokes- show time-of-day variation in their occurrence is a case in point. If scientists knew more about the mechanisms responsible for the rhythmicity of these disorders, they might be able to identify more rational therapeutic strategies to influence these events. Finally, given that dramatic changes occur in the circadian clock system with advanced age, these changes may underlie, or at least exacerbate, the age-related deterioration in the physical and mental capabilities of older adults.
Conclusions
Although researchers in just the past few years have made great advances in understanding the molecular basis of circadian rhythmicity, this progress builds on extensive research carried out in many laboratories during the past 50 years. Within the same period, other researchers in numerous laboratories have elucidated the critical role played by the SCN in the regulation of circadian rhythmicity in mammals and per-haps other vertebrates.
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By Martha Hotz Vitaterna, Ph.D., Joseph S. Takahashi, Ph.D., and Fred W. Turek, Ph.D.
MARTHA HOTZ VITATERNA, PH.D., is a senior research associate in the Center for Functional Genomics, Northwestern University, Evanston, Illinois. JOSEPH S. TAKAHASHI, PH.D., is the director of the Center for Functional Genomics, the Walter and Mary E. Glass Professor in the Department of Neurobiology and Physiology, and an investigator at the Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois. FRED W. TUREK, PH.D., is the director of the Center for Sleep and Circadian Biology and is the Charles T. and Emma H. Morrison Professor in the Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois.
Related Posts:
* Overview of circadian rhythms
* Your internal body clock: the suprachiasmatic nucleus (SCN)
* The study of circadian rhythms
* Glossary of shiftwork terms: shiftwork, sleep, circadian rhythms, and more
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