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Gene Makes for Early Risers

Finding could lead to treatments for people who struggle with shift work, jet lag, study suggests

THURSDAY, Jan. 11, 2007 (HealthDay News) -- Early to bed and early to rise might make you healthy, wealthy and wise, but it's likely the result of a gene mutation, researchers report.

For some time, scientists led by Dr. Louis J. Ptacek, a professor of neurology at the University of California, San Francisco, have been studying several families with a unique sleep problem. These so-called "morning larks" have a condition known as familial advanced sleep phase syndrome (FASPS). People with this condition have a gene mutation that causes them to go to sleep -- in the most extreme cases -- at four or five in the afternoon and wake up at one in the morning, he said.

"FASPS is not hugely common, but it's not rare," Ptacek said. "About 0.3 percent of the population has the mutation."

In its latest research, Ptacek's group has determined how the gene causes the condition, by transplanting the gene into mice to create rodents with FASPS.

"They get up and start running on their running wheels four to six hours before other mice, and they also stop running on their running wheels four to six hours earlier than normal mice," Ptacek said.

In the studies of these FASPS mice, Ptacek's team found that the mutant version of the Period 2 (Per2) clock gene, which is needed to reset the body's central clock in response to light, cannot be chemically changed by an enzyme that controls it. This leads to a reduction in the number of copies of the Per2 gene, and the shift in sleep patterns, the researchers said.

Ptacek thinks these findings may eventually lead to ways to reset humans' internal time clocks and provide new drugs to help deal with sleep problems caused by factors such as shift work or jet lag.

"Very little is known about the human clock," Ptacek said. "Only once we understand what all the gears in the clock are will we be in a position to make decisions about how we might advance or delay our own clocks when we work the night shift or when we travel across time zones."

Ptacek noted that people with FASPS react to the condition differently. Some see it as a problem, while others enjoy being morning larks, he said. "This underscores that FASPS is behavior. Whether you see it as positive or negative depends on your perspective," he said.

The findings are published in the Jan. 12 issue of Cell.

The researchers are also studying people who are night owls and finding there appears to be a genetic link as well, Ptacek said.

One expert thinks that modifying internal clocks -- called circadian rhythms -- is possible but difficult.

"These findings suggest that there are other components of the clock that are not known, that account for different sleep patterns," said Dr. Emmanuel Mignot, a professor of psychiatry and behavioral sciences and director of the Center for Narcolepsy at Stanford University School of Medicine. He co-wrote an accompanying editorial in the journal.

But, other factors also influence sleep and biological clocks, Mignot said. "We know that everything is not genetic," he said. "For example, as people age, they become more and more early birds. That's a natural progression of most people. That's not genetic, because the genes don't change with age."

Mignot said it might be possible to develop drugs that can change the speed of the clock. But, developing a drug that has no other effect than to act on a particular enzyme for a specific purpose may be tough to do. "It's not going to be easy, but it's not impossible," he said.

More information

The National Sleep Foundation can tell you more about sleep.

SOURCES: Louis J. Ptacek, M.D., professor, neurology, University of California, San Francisco; Emmanuel Mignot, professor, psychiatry and behavioral sciences, and director, Center for Narcolepsy, Stanford University School of Medicine, Stanford, Calif.; Jan. 12, 2007, Cell
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