http://www.latimes.com/health/la-sci-sleep-genes-20130302,0,4264278.story
Sleep deprivation has genetic consequences, study finds
Researchers say a lack of sleep affects the function of genes related to stress
and cell renewal, possibly contributing to poor health.
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"It used to be thought that sleep was by the brain, of the brain, for the
brain," says Dr. Charles Czeisler, a Harvard Medical School researcher. "Now
it's recognized that it plays an important role in bodily functions."
(AFP/Getty Images / March 1, 2013)
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By Eryn Brown, Los Angeles Times
March 1, 2013, 11:26 a.m.
Doctors know that being chronically sleep-deprived can be hazardous to your
health. Night-shift workers, college crammers and all the rest of us who get
less than our fair share of zzz's are more likely to be obese and to suffer
cardiovascular woes than people who get a consistent, healthful eight hours.
Now scientists have some new clues about how lack of sleep translates into
disease.
After subjecting 26 volunteers to seven nights of insufficient shut-eye
followed by a marathon all-nighter, researchers detected changes in the way
hundreds of genes were expressed in their bodies. Some genes, including
damage-inducing ones involved in stress reactions, were amplified. Others,
including many that nurture and renew cells and tissues, were turned down.
"It's possible to see how that contributes to poor health," said Colin Smith, a
genomics researcher at the University of Surrey in England and one of the
senior authors of a report detailing the findings this week in the journal
Proceedings of the National Academy of Sciences.
Scientists have long puzzled over the purpose of sleep. For years they focused
on how it influenced the brain, said Derk-Jan Dijk, a sleep and circadian
rhythm researcher at the same institution and the study's other senior author.
But epidemiologists noticed that people who work early in the morning or late
at night — or who lack sleep in general — have higher rates of diabetes, stroke
and high blood pressure, among other ailments. And biologists have discovered
that people who get poor sleep produce more of the stress hormone cortisol and
the appetite stimulating hormone ghrelin, among other biochemical changes.
"It used to be thought that sleep was by the brain, of the brain, for the
brain," said Dr. Charles Czeisler, a Harvard Medical School researcher who is
well-known for his examinations of how poor sleep affects people in a variety
of everyday settings. "Now it's recognized that it plays an important role in
bodily functions."
To learn more about the biological mechanisms at work, Dijk, Smith and
colleagues asked their study volunteers to complete two 12-day-long evaluations.
In one test condition, the subjects — all healthy adults who did not suffer
from sleep disorders — were allowed to stay in bed for 10 hours on seven
consecutive nights. Brain wave scans showed that they slept for an average of
8.5 hours each night, an amount considered sufficient.
In the other test condition, subjects were allowed to stay in bed just six
hours a night for seven nights, and they got an average of only 5.7 hours of
sleep.
At the end of each week of controlled sleep, the researchers kept subjects
awake for 39 to 41 hours, drawing blood every three hours for a total of 10
samples.
Then they analyzed cells in the blood, looking at changes in RNA — the molecule
that carries out DNA instructions, creating the proteins that drive processes
in the body.
They found that losing sleep changed rhythmic patterns in the way genes turn on
and off, disrupting the genes' circadian clock.
Also, overall, 711 genes were expressed differently when people were
sleep-deprived: 444 were turned down, and 267 were amped up.
Further analysis revealed that genes involved in inflammation, immunity and
protein damage were activated, suggesting that tissue harm was occurring after
sleep deprivation. Many of the down-regulated genes, in contrast, were involved
in producing new proteins, cells and tissues. The balanced process of tissue
renewal seemed to be disrupted by insufficient sleep.
Dijk and Smith said they found it striking that the changes were so readily
apparent after just one week.
According to the U.S. Centers for Disease Control and Prevention, 30% of
civilian adults in the U.S. say they get six or fewer hours of sleep. That
suggests that millions of people might be sustaining damage to their bodies.
Scientists who were not involved the study praised its careful design and said
that being able to use blood to assess the molecular effects of sleep
deprivation represented a promising advance for the field.
In the past, many studies of the biological consequences of sleep restriction
were conducted in laboratory animals like mice, with scientists examining gene
expression in tissues from the brain or the liver. For obvious reasons, that's
not feasible with people.
But the ability to use a simple blood test to "tell what time of day" it is in
a person's body could help doctors deal with their sleep-deprived patients,
said Czeisler, who wasn't part of the British research team.
Today, doctors must rely on a patient's self-assessment of how tired he or she
feels. But caffeine "gums up the signal" that tells the brain when it needs
more sleep, fooling people into thinking that they're getting plenty of rest,
Czeisler said.
"This could be an early warning system" that could let doctors know a patient
is at risk for ills related to sleep loss, he said.
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