such as "Introduction", "Conclusion"..etc
In investigating the intricacies of the body's biological rhythms,
scientists at Beth Israel Deaconess Medical Center (BIDMC) have
discovered the existence of a "food-related clock" which can supersede
the "light-based" master clock that serves as the body's primary
The findings, which appear in the May 23 issue of the journal
Science, help explain how animals adapt their circadian rhythms in order
to avoid starvation, and suggest that by adjusting eating schedules,
humans too can better cope with changes in time zones and nighttime
schedules that leave them feeling groggy and jet-lagged.
"For a small mammal, finding food on a daily basis is a critical
mission," explains the study's senior author Clifford Saper, MD, PhD,
Chairman of the Department of Neurology at BIDMC and James Jackson
Putnam Professor of Neurology at Harvard Medical School. "Even a few
days of starvation is a common threat in natural environments and may
result in the animal's death."
The suprachiasmatic nucleus (SCN), a group of cells in the brain's
hypothalamus, serves as the body's primary biological clock. The SCN
receives signals about the light-dark cycle through the visual system,
and passes that information along to another cell group in the
hypothalamus known as the dorsomedial nucleus (DMH). The DMH then
organizes sleep-wake cycles, as well as cycles of activity, feeding and
"When food is readily available," explains Saper, "this system works
extremely well. Light signals from the retina help establish the
animals' circadian rhythms to the standard day-night cycle." But, if
food is not available during the normal wake period, animals need to be
able to adapt to food that is available when they are ordinarily asleep.
In order to survive, animals appear to have developed a secondary
"food-related" master clock. "This new timepiece enables animals to
switch their sleep and wake schedules in order to maximize their
opportunity of finding food," notes Saper, who together with lead author
Patrick Fuller, PhD, HMS Instructor in Neurology and coauthor Jun Lu,
MD, PhD, HMS Assistant Professor of Neurology, set out to determine
exactly where this clock was located.
"In addition to the oscillator cells in the SCN, there are other
oscillator cells in the brain as well as in peripheral tissues like the
stomach and liver that contribute to the development of animals'
food-based circadian rhythms," says Saper. "Dissecting this large
intertwined system posed a challenge."
To overcome this obstacle, the authors used a genetically arrhythmic
mouse in which one of the key genes for the biological clock, BMAL1, was
disabled. They next placed the gene for BMAL1 into a viral vector which
enabled them to restore a functional biological clock to only one spot
in the brain at a time. Through this step-by-step analysis, the authors
uncovered the feeding entrained clock in the DMH.
"We discovered that a single cycle of starvation followed by
refeeding turns on the clock, so that it effectively overrides the
suprachiasmatic nucleus and hijacks all of the circadian rhythms onto a
new time zone that corresponds with food availability," says Saper. And,
he adds, the implications for travelers and shift workers are
"Modern day humans may be able to use these findings in an adaptive
way. If, for example, you are traveling from the U.S. to Japan, you are
forced to adjust to an 11-hour time difference," he notes. "Because
the body's biological clock can only shift a small amount each day, it
takes the average person about a week to adjust to the new time zone.
And, by then, it's often time to turn around and come home."
But, he adds, by adapting eating schedules, a traveler might be able
to engage his second "feeding" clock and adjust more quickly to the new
"A period of fasting with no food at all for about 16 hours is enough
to engage this new clock," says Saper. "So, in this case, simply
avoiding any food on the plane, and then eating as soon as you land,
should help you to adjust -- and avoid some of the uncomfortable
feelings of jet lag."
This research was supported by grants from the U.S. Public Health
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