Study shows internal body clocks become desynchronized under jet-lag conditions

By Fariss Samarrai

A new study demonstrates that internal time clocks in mammals, involving multiple organs, reset at different rates following changes in light cycles. This disruption of the normal relationships among circadian rhythms throughout the body may explain why air travelers experience malaise after crossing several time zones and may point to more serious health issues for shift workers.

Researchers at U.Va.'s Center for Biological Timing, whose findings were reported in the April 28 issue of the journal Science, studied the physiology of the body's reaction to abrupt shifts in cycles of light.

"In nature, light shifts occur slowly as the seasons change," said Michael Menaker, Commonwealth Professor of Biology. "Organisms, therefore, have several months to adjust to the changes. But transmeridian flight is an unnatural event for the body. It causes very abrupt light cycle shifts. The body is not naturally prepared for this sudden change. Once the relationships between the various oscillators are disrupted, the normal function of the organs may be compromised."

Researchers used brain, skeletal muscle, liver and lung tissue from transgenic rats to collect their data.

The rat tissue included a known clock gene indicator from a mouse that is spliced with a glowing "tag" (a firefly enzyme). The tag is activated when the clock gene responds, or is transcribed, during changing light cycles. Menaker and his team were able to "reset" the brain and organ clocks -- the circadian rhythms -- forward by six hours or back by six hours, mimicking the effects of trans-Atlantic travel.

'We demonstrated clearly that both brain and peripheral tissues are rhythmic when they are removed from the animal and held in culture conditions. This is new information, but was suspected. What is surprising is that while the central oscillator in the brain keeps cycling for up to one month, the peripheral tissues rapidly lose their rhythmicity in culture. We now believe the central oscillator in the brain is the key timer that synchronizes the peripheral clock cycles. This helps us understand biologically what happens in an organism when its light cycle is suddenly shifted."

While the symptoms of occasional jet lag may be annoying, the new findings may imply that the physiological effects of rotating shift work could be more serious, he warned.

"Twenty percent of the U.S. workforce are shift workers," he said. "Our findings suggest that frequent irregular light cycle shifts may have biological repercussions. Shift workers, for example, often experience reduced alertness, fatigue, ulcers and poor digestion. We do not know yet the full extent of the health issues that may result from regular disruption of circadian rhythm synchrony.'

According to Menaker, most catastrophic accidents -- such as the Exxon Valdez grounding, and the Three Mile Island and Chernobyl nuclear power plant incidents -- are the result of human error, commonly occurring among shift workers late at night.

"When people are trying to adjust to abnormal sleep and wake cycles, they tend to lose focus, become fatigued more easily and generally don't feel as healthy as they normally would," he noted. "We are showing that a physiological change is occurring. The ramifications for health and performance are real and potentially serious."

U.Va. researchers who conducted the study include Shin Yamazaki, the principal investigator, Michikazu Abe, Gene Block and Menaker. Six researchers from the University of Tokyo and the New Technology Institute in Japan also participated.