Timing Is Everything

Decoding the Meaning of Circadian Rhythms

By Tyler Greer

Every morning, we wake into a world of stress. Some of the tension is conscious: worries over children, jobs, relationships, or money. But these emotional strains are mild compared to the physical stresses we face from the moment our feet hit the floor. Rebooting from a night's sleep is so difficult that the body prepares for the shock with an early wake-up call—from a few billion alarm clocks.

Anticipating and adapting to environmental change is a crucial part of human survival. And if you're going to predict events, it helps to know what time it is. Hence the importance of the biological clock, one of the most well-known examples of the time-based cycles know as circadian rhythms.

“People often think of the biological clock as something that is helpful for sleep, which is one of its functions, but it does far more than that,” says UAB cardiology researcher Martin Young, Ph.D. “These clocks are actually present in essentially every cell in your body. We think that biological clocks prepare the heart before you wake up. They up-regulate the proteins that are protective and will enable the heart to function better in the morning, just like your alarm clock.”

Ongoing research shows that circadian cycles play prominent roles in health and disease. In fact, investigators at UAB have linked the biological clock to everything from heart attacks to psychiatric conditions and diet success.

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The "biological clock" has far more settings than most people realize. Its rhythms affect everything from the quality of sleep to muscle strength throughout the day. (Click image for larger version.)

The brain’s master clock is located in the hypothalamus, in a region called the suprachiasmatic nucleus. Studies have found that this internal timekeeper is involved in the regulation of many physiological processes, including body temperature and digestive tract function. It is usually synchronized to external time signals such as light and dark, but its natural cycles can persist in the absence of such signals: Hop a flight to Calcutta, and you’re likely to still feel sleepy at your normal bedtime, even if it’s high noon in your new location.

Our reactions to this “jet lag” are not uniform, however. Some people quickly adjust with few side effects; others spend their vacations in a bleary-eyed netherworld between sleep and waking.

“If you’re out of synchrony with your environment, or if you have a lack of synchrony between organs, they’re all going to be telling different times—and that’s going to create problems,” Young says. “The cells are all anticipating different stresses, and research shows that a lack of synchrony actually can contribute to disease.”

Clock Watching

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Karen Gamble

UAB psychiatry researcher Karen Gamble, Ph.D., specializes in the secrets of circadian rhythms. She is particularly interested in events that throw these cycles off-kilter, such as shift work. In one study, Gamble and colleagues at Vanderbilt University explored genetic and environmental predictors of adaptation in hospital nurses whose schedules called for three 12-hour day shifts, followed by four days off, and then three 12-hour night shifts. The study found that specific circadian clock genes were associated with a nurse’s typical sleep duration, alcohol and caffeine consumption, and level of sleepiness.

Nurses often live in a state of perpetual jet lag, says Gamble. “It’s like flying back and forth between Tokyo and San Francisco every three days,” she explains. Clock disturbances can greatly disrupt sleep and are a characteristic of many mental health disorders and diseases, including depression and schizophrenia, Gamble says. They also are implicated in illnesses such as the cold and flu. “There is definitely an interplay between chronic jet lag caused by a change in circadian rhythms and immune function.”

Gamble hopes to leverage her circadian research into new treatments. She is now working with colleagues in the Department of Psychiatry to test a drug that could help reset sleep timing in patients with attention deficit hyperactivity disorder who also suffer from insomnia.

Resetting the Clock

Scientists in the UAB Sleep/Wake Disorders Center specialize in treating circadian rhythm disorders and many other conditions. To learn how they treat the two most common circadian disorders, click here.

To keep your circadian clock dialed in, you should set a daily routine—including eating, exercising, sleeping, and waking at the same time each day—and stick with it, says UAB researcher Martin Young, Ph.D. Other tips to get clocks in sync:

Combat jet lag by getting your light-dark cycle and food intake tuned to your new time zone before you leave. Then, when you wake up in your destination, expose yourself to light and eat a big breakfast.

For a pharmalogical solution, you can try the supplement melatonin—an artificial version of a natural body chemical. "It helps you sleep, and it also helps to reset clocks," Young says.

Time to Eat?

UAB research has also identified a role for biological clocks in diet and weight gain. In a recent study, Young and epidemiologist Molly Bray, Ph.D., fed two types of meals to mice. Those who ate a carbohydrate-rich diet in the morning and consumed a high-fat meal at the end of the day saw increased weight gain, adiposity, glucose intolerance, and other markers of metabolic syndrome. Mice who received a high-fat meal in the morning showed little change.

“Fat intake at the time of waking seems to turn on fat metabolism very efficiently, and it also turns on the animal’s ability to respond to different types of food later in the day,” says Bray, the study’s lead author. “The first meal we eat appears to program our metabolism for the rest of the day.” Bray, Young, and UAB nutrition scientist Barbara Gower, Ph.D., are now working on a first-of-its-kind study in human populations.

Entering the Twilight Zone

Circadian cycles extend beyond the 24-hour window, Young notes. In fact, our bodies note the passing of weeks and seasons. There is a complex interconnection between the time of day and serious cardiac events: For example, heart attacks are most likely to occur first thing Monday morning, in winter. “During the week, you often follow a routine—get up at the same time every morning, eat, get dressed, and head into work,” Young says. “Then on the weekend, you’ll stay up later, eat different foods later at night, and sleep in. You disrupt your rhythm. Then Monday morning, you try to wake up early again, but your body clock is out of synch.”

Winter is particularly hard because of the accompanying decline in ambient temperature, and because of the seasonal nature of our body clocks, which run slower in the cold-weather months. “That’s important for hibernating animals because during winter the clocks dampen down, an integral component of the hibernation process,” Young says. Whether you’re a human or a bear, “we’re all slaves to our biological clocks,” he adds. “That’s the truth, unfortunately.”

 

More Information

Martin Young explains his research into the timing of heart attacks (see video below)

 

 

Molly Bray explains the connection between food consumption and time of day (see video below)