Seeking The Link Between Stress And The Body Clock? Just Ask

Researchers in Japan have discovered three genes—Ask1, 2 and 3—linking the ‘internal clock’ of cells and mice to environmental stresses.

AsianScientist (Apr. 10, 2018) – In a study published in the Proceedings of the National Academy of Sciences, scientists in Japan have discovered a link between cellular stress and the circadian rhythm, the internal ‘body clock’ of cells.

Circadian rhythms are found in almost all organisms with sensitivity to light. Problems with circadian rhythms in humans are related to diseases including high blood pressure, metabolic disorders and insomnia. Shift workers and the elderly have increased risk for these diseases as a result of disruption of their circadian clock.

One family of genes—consisting of apoptosis signal-regulating kinase 1, 2, and 3 (Ask1, Ask2, Ask3)—allows cells to adapt to daily changes in environmental conditions by adjusting the circadian rhythm. The effect of environmental or behavioral stresses on the expression pattern of this family of genes remains unclear.

In this study, a research group led by Professor Yoshitaka Fukada and Assistant Professor Hikari Yoshitane at the University of Tokyo, Japan, have found that the expression pattern of Ask1, Ask2 and Ask3 is altered by both sudden and gradual environmental stresses.

The circadian rhythm of normal cells is altered in response to environments with too high or too low salt or sugar concentrations, as well as when they are exposed to excessive oxidative stress. The researchers discovered that cells without the Ask genes did not exhibit changes to their circadian rhythm under these harsh conditions. This suggested that Ask is required for cells to respond to environmental stresses.

“Many researchers in this field have long suspected oxidative stress and circadian rhythms are somehow connected because of the cycles of photosynthesis and DNA replication we see even in ancient organisms,” Fukada explained.

“Photosynthesis requires sunlight and creates free radicals that could damage DNA, so cells postpone DNA replication and cell division until nighttime when photosynthesis has stopped. We are very excited about our results because we can approach the origin of the circadian clock by connecting oxidative stress and circadian regulation through the Ask genes,” he added.

The results in cells were further supported by observations of mouse behavior. Normal mice can alter their waking time the following morning after unexpected light exposure during the night. Mice without Ask genes displayed less ability to synchronize their circadian clock to changes in environmental light-dark cycles.

“The dream is to have a tool to regulate circadian rhythms. Basic science like ours may be useful for later drug discovery work,” said Yoshitane.

The article can be found at: Imamura et al. (2018) ASK Family Kinases Mediate Cellular Stress and Redox Signaling to Circadian Clock.


Source: University of Tokyo; Photo: Shutterstock.
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