Mouse study suggests threat of starvation triggers the switch
THURSDAY, May 22 (HealthDay News) -- New animal research suggests the body's biological clock, which regulates sleep cycles based on the rise and fall of the sun, can be overridden in extreme situations by an internal "food clock."
The finding is based on work with mice and has not yet been tested among humans. But early indications are that, when faced with starvation, the animals automatically adjust their wake-sleep schedule to adapt to the best time to access food.
"In the wild, where starvation is a common threat, this must have evolved as a way for animals to lock onto a new food source, when necessary, to avoid starvation," said study author Dr. Clifford Saper, chairman of the department of neurology at Beth Israel Deaconess Medical Center and a professor of neurology at Harvard Medical School.
Saper and his team reported the findings in the May 23 issue of Science.
They noted that for animals and humans alike, the body's main clock is centered among a group of cells in the brain's hypothalamus region. Referred to as the "suprachiasmatic nucleus", this circadian clock is triggered by visual cues gleaned from the light-dark cycle. Such signals, in turn, activate cells that regulate sleep-wake cycles.
The authors speculated, however, that this standard "master" system could be overridden in situations of extreme duress -- such as starvation.
To test this theory and locate a possible "food clock," the researchers focused on mice genetically altered to lack a gene integral to the master biological clock.
After implanting the mice with transmitters to record body temperature and movement within plastic cages regulated for light and temperature, Saper and his colleagues then restored full light-clock function only to isolated parts of each mouse's brain throughout a rotating series of food deprivation experiments.
Successive two-week long tests were conducted in the context of both a normal light-dark cycle and then a constantly dark setting.
The result: The researchers uncovered the existence of a "feeding clock."
This clock, they noted, kicked into gear and effectively overrode the main light clock after just a single cycle of starvation followed by a re-feeding. The food clock, they concluded, actually hijacked the mouse's circadian rhythms and shifted its sleep-wake cycle to accommodate the need to be awake when food became readily available -- irrespective of the animal's light environment.
Among other things, the discovery of an animal food clock could theoretically lead to an improved method for dealing with jet lag among frequent travelers.
For example, Saper pointed out that while a time zone shift of 11 hours typically burdens our master light-dark clock with a week of difficult jetlag adjustment -- resetting just in time for the trip back home -- careful manipulation of a food clock could potentially render the shift painless and immediate.
"The punch line for humans is that this second clock may be a way for us to control our biological rhythms in shift work or when we travel," he observed. "In other words, it is possible that by fasting during a trip to Japan, then eating a hearty meal when you get there, you may be able to reset your clock much more quickly to the new time."
Ralph Downey III, chief of sleep medicine at Loma Linda University Medical Center at Loma Linda University Children's Hospital in California, described the research as thorough and interesting.
"It provides valuable insight into other possible clocks that time our behavior and time our sleep," he noted. "And it provides a little more complexity to our biology in terms of why we do things when we do them. So, we can see that there's a master clock, but interconnected with that clock are other clocks -- other spinning wheels. And while under normal circumstances the master clock works nicely, in extreme situations, the master clock can be overridden, which is a very adaptive thing that makes a lot of sense from an evolutionary perspective."
While equally intrigued, Dr. Emmanuel Mignot, director of the Stanford University Center for Narcolepsy, cautioned that the current research with animals still needs to be replicated in humans.
"However, this work opens up the idea that while there certainly is a central light clock, and clearly light does 90 percent of the regulatory job, other factors may come into play," he said.
"In fact," Mignot added, "I would say that in most cells in your body, you have a clock, and most of the time, these clocks talk to each other. Because the body is always prepared to anticipate different changes that should happen at certain times of the day. So, I wouldn't be surprise if there's a clock in your skin to anticipate light in the day, and a clock in your kidneys, so you are prepared to go the restroom. It's not just about being tired. It's pretty much every function that's regulated by the time of the day."
For additional information on sleep and the circadian rhythm, visit the National Sleep Foundation.
SOURCES: Clifford Saper, M.D., Ph.D., chairman, department of neurology, Beth Israel Deaconess Medical Center, and professor, neurology, Harvard Medical School, Boston; Ralph Downey III, Ph.D., chief, Sleep Medicine, Loma Linda University Medical Center, Loma Linda University Children's Hospital, Calif.; Emmanuel Mignot, M.D., professor, psychiatry and behavioral sciences, and director, Stanford University Center for Narcolepsy, Stanford University School of Medicine, Palo Alto, Calif.; May 23, 2008, Science
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