The researchers at Oxford University and F. Hoffmann La Roche have identified a mechanism that limits the ability of the body clock to adjust to changes in patterns of light and dark.
They show that if you block the activity of this gene in mice, they recover faster from disturbances in their daily light/dark cycle that were designed to simulate jet-lag.
The study was funded by the Wellcome Trust and F. Hoffmann La Roche, and is published in the journal Cell.
Nearly all life on Earth has an internal body clock that keeps us ticking on a 24-hour cycle, synchronising a variety of bodily functions such as sleeping and eating with the cycle of light and dark in a solar day.
When we travel to a different time zone, our body clock eventually adjusts to the local time. However this can take up to one day for every hour the clock is shifted, resulting in several days of fatigue and discombobulation.
In mammals, the body clock – or circadian clock – is controlled by an area of the brain called the suprachiasmatic nuclei (SCN) which pulls every cell in the body into the same biological rhythm. The SCN receives information from a specialised system in the eyes which senses the time of day by detecting environmental light, and synchronises the clock to local time.
Until now, little was known about how light affects activity in the SCN to ‘tune’ the body clock, and why it takes so long to adjust when the light cycle changes.
To investigate this, the Oxford University team led by Dr Stuart Peirson and Professor Russell Foster examined the patterns of gene expression in the SCN of mice following a pulse of light during the hours of darkness.
They identified around 100 genes that were switched on in response to light, revealing a sequence of events that retune the circadian clock.
Among these, they identified one molecule, called SIK1, that acts as a brake to limit the effects of light on the body clock. When they blocked the activity of SIK1, the mice adjusted faster to changes in light cycle.
Dr Peirson, of Oxford’s Nuffield Laboratory of Ophthalmology, explained: ‘We’ve identified a system that actively prevents the body clock from re-adjusting.
‘If you think about it, it makes sense to have a buffering mechanism in place to provide some stability to the clock. The clock needs to be sure that it is getting a reliable signal, and if the signal occurs at the same time over several days it probably has biological relevance. But it is this same buffering mechanism that slows down our ability to adjust to a new time zone and causes jet lag.’
Disruptions in the circadian system have been linked to chronic diseases including cancer, diabetes and heart disease, as well as weakened immunity to infections and impaired cognition. More recently, researchers have found that circadian disturbances are a common feature of several mental illnesses, including schizophrenia and bipolar disorder.
‘We’re still several years away from a cure for jet-lag, but understanding the mechanisms that generate and regulate our circadian clock gives us targets to develop drugs to help bring our bodies in tune with the solar cycle,’ said Professor Foster, director of the recently established Oxford University Sleep and Circadian Neuroscience Institute which is supported by the Wellcome Trust.
‘Such drugs could potentially have broader therapeutic value for people with mental health issues.’