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OUR CIRCADIAN RHYTHMS ARE MANY:
“Clock genes” in the liver anticipate mealtimes // Those in the heart, our awakening // A master clock to coordinate these and thousands of others // All of which can fall out of sync, to ill effect

Circadian Rhythms: The Timekeepers Within

By Anita Slomski // Photographs by Kevin Twomey // Spring 2012
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Kevin Twomey

Given their druthers, about 40% of people would go to bed around 11:30 p.m. and wake about 8:30 a.m. But some 10% would rather turn in at 3 a.m. or even later and sleep until mid-morning, according to an online survey of 125,000 people by Till Roenneberg, who heads the Centre for Chronobiology at the Institute for Medical Psychology at the Ludwig-Maximilians-Universität in Munich. And according to a study by the Northwestern University Feinberg School of Medicine, those night owls also tend to be overweight and to sleep fewer hours than those with more normal schedules. “Late sleepers” in the study consumed only 248 more calories a day—the equivalent of about three ounces of lean ground beef—than those who ate dinner at 7 p.m. and were asleep by 12:30. But the late sleepers had an average body mass index of 26 compared with 23.7 for early sleepers. For someone five feet eight inches tall, that’s the difference between weighing about 171 pounds and 156 pounds. “Our results show that the circadian system plays an important role in metabolism,” says Kathryn Reid, research assistant professor of neurology at Feinberg.

In fact, circadian rhythms, roughly corresponding to a 24-hour day (the Latin roots of circadian mean “about a day”), affect cells and biological processes throughout the body. It has long been known that all plants and animals, including humans, have internal clocks and that disruptions in sleep patterns can lead to problems. People who work the overnight shift, for example, have a greater incidence of diabetes, obesity, hypertension, cardiovascular disease and cancer than people who are awake during the day and sleep at night. But now researchers think that chronic (though less drastic) changes may also put people at risk. By catching up on e-mail correspondence at midnight or getting too little sleep during the week and trying to make up for it by rising later on weekends, people may overstress their bodies and make themselves more susceptible to illness. And those already vulnerable because of age or health problems could fare even worse if they fall out of phase with their circadian systems.

But even though we’ve known for some time that circadian rhythms have a direct impact on human health, much less has been understood about how the internal timekeepers in the brain and other organs communicate and what happens to put them out of sync. The most recent discoveries involve so-called clock genes, first identified in 1994, that ramp up and down the production of essential proteins that prepare cells to react to environmental stimuli. The liver, for example, relies on its clock genes to predict when food will be consumed so its cells will be revved up to metabolize and store nutrients. “If people eat when the liver isn’t anticipating nutrients coming into the body, it can’t regulate sugar and fat metabolism properly,” says Mitchell A. Lazar, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine at the University of Pennsylvania. “That dissonance can lead to extra fat in the liver and contribute to diabetes and lipid disorders.”

For now, most circadian experiments fall into two categories. In basic research with animals, scientists manipulate genetic clocks to gauge the impact on the organs. Meanwhile, human studies alter volunteers’ schedules to measure what happens when normal patterns of eating and sleeping are upended. The results of both lines of research could eventually lead to better disease treatments. For example, there’s already evidence that finding optimum times to administer chemotherapy or other treatments can make the drugs less toxic and more effective. “Because internal clocks are so enmeshed in regulating cells, they present many opportunities to therapeutically target genes important in cancer and even neurologic disease,” says Joseph Takahashi, professor of neuroscience at the University of Texas Southwestern Medical School in Dallas.

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Circadian Rhythms: Turns for the Worse

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Understanding circadian rhythms may help doctors time treatments for optimum effect.

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1. “The Genetics of Mammalian Circadian Order and Disorder: Implications for Physiology and Disease,” by Joseph S. Takahashi et al., Nature Reviews/Genetics, October 2008. In the future, say the authors of this review article, treatment for diabetes and obesity may include altering circadian rhythms because they are so “intimately linked” to metabolism and cell proliferation.

2. “Influence of the Circadian System on Disease Severity,” by Mikhail Litinski et al., Sleep Medicine Clinics, June 1, 2009. The authors present fascinating evidence not only that misaligned circadian clocks contribute to disease but also that normal fluctuations in circadian rhythms can make people with certain disorders more vulnerable to adverse events at particular times of the day.

3. “Role of Sleep Timing in Caloric Intake and BMI,” by Kelly G. Baron et al., Obesity Journal, April 2011. In one of the few studies that examine weight and sleeping patterns in humans, Baron and colleagues found that people who went to bed late ate more of their calories after 8 p.m. and consumed more junk food than did people who went to sleep at a more typical time. Late sleepers ate on average 248 more calories per day—which, after a month, would add two pounds to their weight.

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