February 28th, 2015
Almost all animals have an internal body clock, keeping several functions, including sleeping and eating, synchronised with the light/dark cycle around a 24-hour day. Humans are no exception. If we have to travel across the globe to a new time zone, our body clock takes about a day to adjust to the new time for every hour the clock moves.
This may result in several days of feeling tired and ‘out-of-tune’, known as jet-lag. Not surprisingly, it’s considered a nuisance, but how much do we really understand about this phenomenon?
Now, a team of researchers, led by Prof Russell Foster, Director of the Oxford University Sleep and Circadian Neuroscience Institute, unveiled a new mechanism that could potentially explain why we recover so slowly from jet-lag.
In mice, about 100 genes involved in fine-tuning the internal clock were switched on when these animals were exposed to a pulse of light during the night. However, at the same time, a counter-acting mechanism turned those same genes off, limiting the effect of light.
“We’ve discovered a completely new pathway, where light can turn genes on and start to shift the clock to the new light/dark cycle”, explains Prof Foster, but “you can’t get huge gene expressions, because there’s a break on it”.
Prof Foster explains why it makes sense to have such a break: Our body needs to be convinced the new dark/light cycle has some biological significance, occurring over a few days. This means the same mechanism that maintains our body clock stable, delays our ability to adjust quickly to a new time zone.
The study published in Cell also identified a possible target for new therapeutic drugs – a protein called SIK1 – to help us adapt quicker to changes in our internal body clock. When researchers managed to reduce the activity of this protein, which is involved in the break mechanism, mice could adjust to a shift of six hours within a single day. “It was extraordinary”, says Prof Foster, “we’ve essentially turned that break off”.
“There are very few ways in which you can change the clock”, continues Prof Foster, but now “we could actually envisage a way to get rid of jet lag”, by developing drugs to “manipulate this particular break, and turn it off or on, allowing us to adjust to a new time zone much quicker”.
Jagannath A, Butler R, Godinho SI, Couch Y, Brown LA, Vasudevan SR, Flanagan KC, Anthony D, Churchill GC, Wood MJ, Steiner G, Ebeling M, Hossbach M, Wettstein JG, Duffield GE, Gatti S, Hankins MW, Foster RG, & Peirson SN (2013). The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock. Cell, 154 (5), 1100-11 PMID: 23993098