Resetting the master body clock

JET LAG can last for up to a week, even though the brain's master body clock can reset itself in just a day. New research suggests that this could be because individual body clocks in the lungs, muscles and liver adapt at different rates, and may be thrown out of kilter for days.

Hajime Tai at the University of Tokyo, Japan and Michael Menaker at the University of Virginia, Charlottesville, Virginia and their team used genetically modified rats to monitor the impact of time shifts on body clocks or `circadian rhythms' in different organs.

The researchers engineered the rats so that their bodies produced a protein called `luciferase' instead of another protein, `Per1', which is central to circadian rhythms.

Luciferase is the enzyme that gives fireflies their glow, so the rats' cells actually lit up in step with their body clocks.

As they report in Science, the team reared these rats with twelve hours light and twelve hours darkness per day.

When they examined cells from the rats' `suprachiasmatic nuclei' - the brain region that acts as the master clock - they saw a strong, regular twenty-four-hour rhythm that lasted up to a month outside the body. Cells from the lungs, muscles and liver also glowed in a daily rhythm, but these oscillations petered out after four or five days.

Clearly, there are several clocks ticking away in rats' bodies, but how do these clocks cope with a change in `time zone'? To find out, the researchers subjected the rats to a sudden six-hour delay in their daily cycle, rather like the jump caused by flying from Paris to New York.

After one day on the new time-zone, the rats' brains adapted fully and their lungs and muscles were not far behind, having already compensated by four hours.

The liver, though, was a different story - it didn't shift its rhythm at all. Even in rats given six days to adjust to the new regime, the liver only managed to compensate by three and a half hours while other organs caught up completely. In fact, after sixteen days, the liver still did not quite regain its normal cycle.

Tai's group believes that resetting the clocks throughout the body can take weeks, leaving metabolic processes uncoordinated. This slow rate of synchronization is no problem when an animal is adapting to the passing seasons. But, if the same occurs in humans, it might explain why sudden jumps such as long-haul flights or shift changes at work cause us such discomfort.

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