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.


eryn.brown@latimes.com