Body clock reset clue discovered

A small molecule may have a big role in making the body clock tick, say Cambridge University researchers.

Studies in mice have shown cAMP - a common signalling molecule - is involved in keeping the body clock "rhythms" going.

The team hope to develop drugs that target cAMP to help shift workers, frequent flyers or those with sleep disorders reset their body clocks.

But the research, published in Science, is still a long way from the clinic.

The body's internal clock is a highly sensitive mechanism able to anticipate changes in the environment and regulate a host of body functions, from sleep patterns to metabolism and behaviour.

Disruption of these "circadian" rhythms have been shown to be linked with insomnia, depression, heart disease, cancer and neurodegenerative disorders.

At the beginning of the circadian day, genes are switched on which then produce proteins which in turn go on to switch off the same genes at the end of the day.

The proteins are broken down over the circadian night and the process starts all over again in the morning.

Researchers at the Medical Research Council Laboratory of Molecular Biology discovered that cAMP not only helps regulate the production of these proteins but that its own rhythm is also regulated by this "loop".

In laboratory experiments in cells the proteins were engineered to light up so the researchers could easily monitor the circadian rhythms depending on how much protein was present dependent on the activity of cAMP.

Slow down

Study leader Dr Michael Hastings said in mice who by a quirk of genetics had a 20-hr body clock, they were able to reset the clock to 24 hours by using known compounds that are known to slow down the action of cAMP.

"What's neat about cAMP is that it is very easily controlled by different medicines and compounds."

He added the MRC had filed a patent for developing ways to manipulate cAMP with regards to body clock but there were 15 to 20 years of experiments before any drug would be available for human use.

"If you're flying to California it takes eight to nine hours and the body clock can adjust by one hour for each day so it takes about a week and then you have to come back.

"What we need to do is slow down the clock for that first day from 24 to 36 hours so you would already be in sync with California time," he said.

Dr Neil Stanley, a sleep expert at Norwich University Hospital, said the body clock was an incredibly complex system.

"This is very interesting from a biological basis but the perils and pitfalls of trying to develop new methods for regulation of sleep are great.

"For example melatonin hasn't really fulfilled its promise and it's been harder to use it usefully than people once hoped."

RESOURCE/SOURCE:  news.bbc.co.uk on May 15, 2008