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Body's clocks each reset at own pace, jet lag study finds

If a trip across the ocean or a new shift at work can make you feel like your body is out of sync, science is now on your side.

New research on rats suggests that after shifting schedules too far ahead or behind, certain organs get back on track before others. If the same holds true for people, it could explain why jet lag and shift work can make people feel so out of whack.

In the new study, published Friday in the journal Science, researchers measured how long it took for biological clocks in various organs of rats to get back on schedule after a simulated trans-Atlantic trip. The brain clock got back on track first, then the lung and muscle clocks. But the liver clock was not back on track even after six days. Because the biological clocks that keep organisms in tune with the sun's rising and setting are quite similar in every species, people probably get as out of step as the rats.

"I think there are going to be differences [between rats and people], but I think the differences are likely to be minor," said Michael Menaker, a biologist who worked on the new research.

Research on biological clocks has exploded in the last few years. These clocks - networks of molecules and genes inside cells - have been found throughout nature, in organisms as simple as bacteria and as complex as people.

Biological clocks in people control not just sleep, but body temperature, organ function, hormone levels and cell division. Just before waking, for example, the heart beats faster and the kidneys start pumping.

Scientists believe that a person's master clock is in the brain. Clocks in the rest of the body's cells, the theory goes, listen to the master brain clock to keep their own rhythm on track. But this resetting apparently doesn't go smoothly after extreme schedule changes.

Why each tissue in the body has a clock is still a mystery. The liver, for example, can detoxify alcohol better in the early evening than late at night or early in the morning. It may make sense to happy-hour drinkers, but scientists still don't have an explanation.

In the new research, Dr. Menaker and his colleagues at the University of Virginia in Charlottesville, and scientists at two institutions in Japan, used a special strain of lab rats to test the effects of a severe case of jet lag. The rats had been genetically engineered in a way that let scientists measure individual organs' clocks in action.

Boarding the rats onto an intercontinental flight would not have been practical. So instead, the scientists simulated a six-hour time zone change by leaving the lights on longer - or turning them off sooner - than normal. The scientists examined the rats' organs at either one or six days after the shift to see whether the organs' own clocks had been reset.

The master clock in the brain reset within a day, Dr. Menaker said. But the liver wasn't resynchronized with the on-and-off schedule of the laboratory lights even after six days. Because the liver produces factors to help digest food, a liver out-of-rhythm with a meal schedule might make for bad digestion, Dr. Menaker said.

Scientists expected the brain and the various body clocks to reset themselves, said Joseph Takahashi, a biological clock researcher at Northwestern University in Evanston, Ill.

"What we didn't expect is for the whole body to be much slower, and for different organs to adapt at different rates," he said. "A six-hour shift could be simple if our whole body was shifting in register. But everything is disorganized."

There's actually no reason to expect the body should be able to adjust quickly to a big jump in time zones, or a dramatic change in work shift, said Steven Kay, a biologist at the Scripps Research Institute in La Jolla, Calif.

For most of human history, we've needed to reset our clocks only to adjust to day-length changes throughout the year, he said. But there was little need to reset the clock quickly before societies became industrialized and long-distance jet travel became possible.

More studies need to be done to see exactly what shift work and jet lag do to different organs in people, Dr. Menaker said.

Dr. Kay said discovery of a clock component recently reported by Drs. Menaker and Takahashi, also in Science, might help scientists come up with drugs to set clocks forward or backward as needed.

Dr. Menaker said he hopes awareness about the effects of shift work will make it out of science journals and into society.

A 1997 report from the Bureau of Labor Statistics found that one in five employed U.S. citizens works a schedule that is not a fixed daytime one.

Shift work is like continuous jet lag, Dr. Menaker said.

"That's really the centrally important public health problem. Jet lag is just annoying, but shift work is probably serious," he said.

Public awareness of biological clocks will grow, Dr. Menaker said, as physicians learn which time of day is best for administering drugs like chemotherapy.

"The administration of drugs is going to be put under time control in order to maximize the efficiency of what you're trying to do and minimize the side effects," he said. "The effect of what you're trying to achieve and side effects have different rhythms."
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