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Tired? Biological clock out of whack? Blame genes and epigenetics

| December 10, 2014
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This article or excerpt is included in the GLP’s daily curated selection of ideologically diverse news, opinion and analysis of biotechnology innovation.

What controls your biological clock and can we tinker with it?

Researchers at the RIKEN Center for Developmental Biology megaplex as well as the Universities of Hiroshima, Osaka, Japan Science and Technology Agency, in coordination with the University of Michigan recently reported a novel ‘negative feedback’ system in our genes that allows for our finely-tuned circadian rhythms. This new internal clock protein, expressed by our genes, appears to sensitively modulate based on our lifestyles and “integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock.”

Our daily biological clock—our “circadian rhythms”—are so-named because their Latin root derives from ‘circa’ (about) and ‘dian’ (day, from diem). For those who have tried to get a normal night’s sleep after traveling and changing time zones it comes as no surprise that it’s a very finely-tuned and sensitive apparatus. These new data offer a window into how complex it really is.

When we see light (especially sunlight, given the breadth of the spectrum), the specialized ganglion cells on the retina transmit this information directly to a region of the brain called the suprachiasmatic nuclei (SCN). These nuclei represent a distinct group of cells within the hypothalamus, which is itself responsible for a litany of metabolic regulatory factors in our bodies. In animal models in which this region has been excised, or in humans who have had damage to this region, the sleep-wake cycle is non-existent.

The disruption of our normal circadian rhythms has been implicated in cancer, chronic disease, and psychiatric conditions. In this recent research, the authors used ‘circadian period of locomotor activity’ as their measurement for sleep-wake cycle duration. The authors named the gene they identified as responsible for these findings “Chrono.” It is 375 amino acids in size and ‘well-conserved,’ which is a marker of its biological importance – the more highly-conserved a gene is, the more fundamental it is usually considered to be.

The researchers found evidence that Chrono’s functionality can be triggered by stress. It appears to function as a circadian repressor (reduces activity in mammals) and seems to be regulated independently of other previously-found circadian clock cycles. It does so in a physiological response-dependence (that is, the more behavioral stress one is under should translate into greater activity repression due to the Chrono gene). The research begs for further study to be done on how Chrono interacts with the hypothalamus-pituitary-adrenal (HPA) axis, which is a well-known factor in behavior and stress-response.

This novel evidence will likely usher in future studies focused on the potential for enhanced treatments for insomnia, stress-related sleep disturbances and circadian rhythm problems – together which affect an estimated 40 million people in the U.S. alone, and cost $16 billion annually.

As we underscore frequently at the GLP, we are our genes, and the better this is understood, the more we are able to intelligently respond to the challenges we face as individuals and society – and sleep is something that occupies between about 25 percent – 38 percent of our time every day.

Ben Locwin, PhD, MBA is a contributor to the Genetic Literacy Project and is an author of a wide variety of scientific articles for books and magazines. He is also a researcher and consultant for a variety of industries including food and nutrition, pharmaceutical, behavioral and psychological, and academic.

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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