The enzyme casein kinase 1epsilon (CK1epsilon) controls how easily the body’s clockwork can be adjusted or reset by environmental cues such as light and temperature, according to researchers from The University of Manchester. The discovery, which is being published in Current Biology, could provide a solution for alleviating the detrimental effects of chronic shift work and jet lag.
In mammals, circadian clocks are found in most cells and tissues of the body and orchestrate daily rhythms in our physiology, including our sleep/wake patterns and metabolism.
The research identifies a new mechanism through which circadian clocks respond to light inputs. During the study, mice lacking CK1epsilon, a component of the clock, were able to shift to a new light-dark environment (much like the experience in shift work or long-haul air travel) much faster than normal.
The research team went on to show that drugs that inhibit CK1epsilon were able to speed up shift responses of normal mice, and, critically, that faster adaption to the new environment minimized metabolic disturbances caused by the time shift.
“We are not genetically pre-disposed to quickly adapt to shift work or long-haul flights, and so our bodies’ clocks are built to resist such rapid changes,” says Dr David Bechtold, who led The University of Manchester’s research team, in a release. “Unfortunately, we must deal with these issues today, and there is very clear evidence that disruption of our body clocks has real and negative consequences for our health.”
He continues: “As this work progresses in clinical terms, we may be able to enhance the clock’s ability to deal with shift work, and importantly understand how maladaptation of the clock contributes to diseases such as diabetes and chronic inflammation.”
This work, funded by the Biotechnology and Biological Sciences Research Council, was undertaken by a team from The University of Manchester in collaboration with scientists from Pfizer led by Dr Travis Wager.