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Researchers identify 'jet lag gene'

Monday 2 September 2013

"Could new discovery lead to a cure for jetlag?" asks the Daily Mail, which is one of several news sources to report on the discovery of a gene that prevents us from adjusting to new time zones. 

When flying long-haul, it can take some travellers several days before their sleeping patterns adapt to a new time zone.

New research has identified a protein in the brain called Sik1, which is believed to be involved in regulating our body clock.

The study, carried out in mice, found that Sik1 works by slowing down how fast we adjust to a sudden change in time zone.

Researchers found that by reducing the levels of Sik1, the mice adapted more quickly when their sleep time was shifted six hours – the equivalent of a long-haul flight from the UK to India.

It is thought Sik1 plays an important role in preventing the body clock from being upset by small or temporary disruptions, such as artificial light.

This study has identified the Sik1 protein as another piece of the puzzle in how the body clock works. Further studies are needed to identify or develop drugs that can affect the function of Sik1 and test their effects in mice.

These studies will need to show that such drugs are acceptably effective and safe before they could be tried in humans. Scientists need to understand more about what effect stopping Sik1 would have on the human body. This means that the possibility of a "cure" for jet lag is still a distant one.

Where did the story come from?

The study was carried out by researchers from the University of Oxford and other research centres in the US, Germany and Switzerland. It was funded by The Wellcome Trust, F. Hoffmann-La Roche, the National Institute of General Medical Sciences, and the National Science Foundation.

The study was published in the peer-reviewed scientific journal Cell.

The news sources generally covered this story appropriately, with The Independent online illustrating the story with a picture of mice to show readers at a glance that this was an animal study.

What kind of research was this?

This was a laboratory and animal study that aimed to identify the proteins that play a role in how light regulates our body clocks.

When our eyes are exposed to light at dawn and dusk, the retina sends signals to a part of the brain called the suprachiasmatic nuclei (SCN). A body clock "pacemaker" in this region sends out signals that synchronise the body clocks in each individual cell in the body.

It is thought jet lag arises because of the time it takes for this system to adapt to the change in the light-dark cycle in a new time zone. Human behaviour is believed to adapt to a new time zone by about an hour a day.

Although some of the proteins involved in controlling the body clock in the cells are known, the proteins in the SCN involved in setting the body clock in response to light are less well understood. The researchers in the current study wanted to identify these proteins.

This type of experiment would not be possible in humans, so animal studies are needed. Animals also have body clocks, although they may be "set" to different timings to humans. For example, mice are nocturnal while humans are not. Despite these differences, the proteins involved in these processes in humans and other animals such as mice are very similar.

What did the research involve?

The researchers looked at which genes are switched on or off in the SCN in mice in response to exposing them to light at night. By doing this, they were forcing the mice's body clock to start to reset itself.

Once they identified these genes, they carried out a range of other experiments to test their role in setting the body clock. This included testing how the mice's body clocks were affected when the levels of these proteins were reduced. They did this by injecting a chemical near to the SCN to reduce the amount of a specific protein being produced.

They then assessed how these mice differed from normal mice in their response to a change in the normal light cycle by six hours, mimicking the effect of moving time zones and jet lag.

What were the basic results?

The researchers identified a large number of genes (536 genes) that were switched on or off in the SCN in response to light exposure at night. Most of these genes were switched off (436 genes), while 100 were switched on.

By looking at what is already known about these switched on genes, they identified a gene called Sik1 as being potentially involved in resetting the body clock. For example, previous studies had shown that switching off Sik1 in cells affected their "clock", so the cells had a 28-hour cycle instead of the normal 24 hours.

The researchers suspected that Sik1 could be putting a brake on the body clock being reset. Experiments in cells in the laboratory suggested that this could be the case, so researchers went on to test their theory in mice.

They found that reducing the amount of Sik1 protein in the SCN made the mice adapt faster to a new time zone (a light-dark cycle shifted by six hours). This meant that these mice more quickly showed activity patterns that matched their shifted day pattern than normal mice, who took longer to move away from their previous activity pattern.

How did the researchers interpret the results?

The researchers concluded that their experiments in cells and mice showed that the Sik1 protein acts to "put the brakes on" the body adapting to a new light-dark cycle. They suggest that this may be to protect the light-reactive SCN from sudden and large changes in the body clock, which might lead to its clock being out of sync with the rest of the body.

The authors say that in modern life disruption of normal sleep and body clock rhythms is common, for example in people doing shift work or after long-haul travel. They say that knowing more about how the body clock works may help develop drugs to help reset the body clock in people with these disruptions.

Conclusion

This study has identified the Sik1 protein as another piece of the puzzle in how the body clock works. Although there are many differences between humans and other animals such as mice, the roles of the proteins in our cells and how they interact are very similar. This allows researchers to gain insight into our biology using studies in other animals that they would not be able to do in humans.

Further studies will be needed to identify or develop drugs that can affect the function of Sik1 and test their effects in mice. These studies will need to show that such drugs would be effective and safe before they could be tried in humans.

As the authors note, this protein is likely to exist to help prevent our body clocks changing too fast and we need to understand more about the consequences of stopping it doing this. Despite these findings, the possibility of a "cure" for jet lag is still only a distant one.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

'Molecular basis' for jet lag found.

BBC News, 30 August 2013

Gene discovered that could cure jet lag.

The Daily Telegraph, 30 August 2013

Could new discovery lead to a cure for jetlag?

Daily Mail, 29 August 2013

One step closer: the pill that brings jet lag down to earth.

The Independent, 29 August 2013

Links to the science

Jagannath A, Butler R, Godinho S, et al.

The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock

Cell, Volume 154, Issue 5, 1100-1111, August 29 2013