Disruptions to our circadian rhythm, the 24-hour clock that drives sleeping and wakefulness, affect our bodies in more ways than previously believed.
New research shows that each of our organs contains cells with their own circadian-clock genes that help bodily processes, such as digestion, operate with maximum efficiency at certain times of day.
When a person’s circadian clock is thrown off—by jet lag or shift work or eating at the wrong time—it can, over time, contribute to weight gain and depression. It may even increase the likelihood of heart and liver problems.
“If you disturb that 24-hour organization, you’re going to have a disruption of function within the tissue,” says Fred Turek, a biology sciences professor and director of Northwestern University’s Center for Sleep and Circadian Biology, in Evanston, Ill.
10%: of the genes in our body tissue operate on a 24-hour rhythm, according to scientists.
The brain used to be thought of as the body’s master clock, sending signals telling organs when to operate. But over the past decade or so, as scientists discovered clock genes in cells in different organs in the body, the brain has come to be seen as the conductor of an orchestra. Each organ operates on its own internal clock, producing enzymes and molecules at different levels depending on the time of day; the brain works to make sure all the clocks are synchronized. Dyssynchrony between the brain and the rest of the organs, or between individual organs, can lead to problems. For example, if the pancreas is out of sync with the liver, insulin production may be too low or too high, Dr. Turek says.
The ubiquity of clock genes in the body has led to a burgeoning field of research focused on how disruptions in circadian rhythm may contribute to disease, and whether normalizing circadian rhythm within cells could help prevent or treat conditions including colitis, diabetes and obesity. Some researchers are conducting trials to see whether there is an optimal time of day to eat in order to gain less weight.
The clock genes appear to have a particularly strong influence on metabolism and how the body handles fat and sugar. For much of the past decade, Dr. Turek and his colleagues have been studying the way these genes interact with fat and how they contribute to obesity, diabetes and digestive conditions like colitis.
Like Clockwork
Click below to see a typical circadian-clock cycle based on an average sleep time:
View Full Image
In 2005, they demonstrated that mice with a mutation to a clock gene in the brain’s “suprachiasmatic nucleus”—the region thought responsible for synchronizing circadian rhythm across the body—had a disrupted feeding pattern.
The mice ate more at all hours of the day, rather than primarily in the evening, when they are typically awake. These mutant mice were obese and had a number of metabolic problems, including high cholesterol and high blood sugar. The findings were published in the journal Science.
Then the researchers found something startling: It wasn’t just that the mice’s clock-gene mutation changed their behavior, but also that their behavior influenced the clock genes.
Eating a high-fat diet appeared to change the circadian-clock genes in a part of the brain, the liver and in fat tissue. In a later study, the group showed that nocturnal mice fed a high-fat diet only during the daytime, when they are supposed to be sleeping, gained more weight than mice fed during the dark phase, even when they ingested the same number of calories.
It isn’t clear exactly how disruptions in circadian rhythm could influence body weight. One theory is that at certain times of day, intestinal bacteria may be more or less active at breaking down food into molecules to be absorbed by the intestine. Eating fat at a time when the bacteria are less active could lead to poorer food breakdown and more fat stored, Dr. Turek says.
Dr. Turek’s team is also studying the intestinal condition known as colitis. Symptoms, including bouts of intense diarrhea, come and go in cycles—an observation that led Dr. Turek and his colleague, Ali Keshavarzian of Rush University Medical Center, to ask if circadian rhythm might play a role.
In a study published in 2008, they gradually shifted the sleep-wake cycle of healthy mice every five days for three months and showed that the animals had no changes in weight or intestinal distress. But when given a solution that induced colitis symptoms, mice whose sleep cycle had been shifted fared far worse, losing 25% of their body weight; mice on a normal circadian routine lost only about 10% of body weight.
In a separate study published in 2009 in Sleep Medicine, Dr. Turek’s team found that mice whose sleep was deprived had worse inflammation and slower recovery compared to mice in a control group.
“If you have your circadian clock disrupted, it may not be a problem,” Dr. Turek says. “But it may be a problem if you’re pregnant, or if you’re eating much more at the wrong time of day, or if you’re getting the flu.”
Other researchers have looked at the effect of clock genes on the liver. Steve Kay, dean of the biological-sciences division at the University of California, San Diego, and his colleagues showed that a particular clock gene shuts down excess glucose production in the liver.
A team from the University of Pennsylvania, led by medicine and genetics professor Mitch Lazar, recently found a clock-gene mechanism that reduces the production of fat in the liver at certain times of the day. Such findings suggest manipulating these clock genes could have implications for diabetes or fatty liver disease.
Other researchers, like Martin Young at the University of Alabama at Birmingham, are studying clock genes in the heart and have found evidence that circadian rhythm appears related to lipid production, like triglycerides, which could stress the heart and contribute to cardiac disease.
The easiest of the body’s circadian clocks to reset is that of the brain, Northwestern’s Dr. Turek says. Getting enough sleep—seven to eight hours—and ideally sleeping and waking at about the same time each day, even on weekends, is important to keep the sleep-wake cycle in tune.
It doesn’t appear that the seven to eight hours need be continuous at night, but consistently more sleep is better than less, says Dr. Turek. Eating and exercising regularly, but not close to bedtime, also are important to the sleep-wake cycle, he says.
In a case where the rhythm of a particular organ is out of sync with other organs, realignment is more difficult. It may not possible for an individual to control by changing their behaviors, but opens up the possibility of novel ways of treating disease.
“Now, perhaps in some patients, the reason they’re developing disease and other disorders is a biological clock that’s not functioning,” says UC San Diego’s Dr. Kay. “Now we have a number of new avenues for developing treatments.”
Write to Shirley S. Wang at shirley.wang@wsj.com
According to a recently released study published in the Archives of Internal Medicine this week, there is little to no health risk in using the full body scanners at the airports.
