The tick-tock of your body clock

by Daphne Howland

Circadian rhythms are 24-hour cycles of behavior or biological activity that are regulated by an organism's "internal clock" and are synchronized by light/dark cycles and other daily environmental cues.

The ancients understood that some biological workings were coordinated with the timing of day and night. Nineteenth-century thinkers postulated that God himself was a clockmaker. But the idea of an internal clock remained controversial as late as 1960. Since then, scientists have located this "timing" mechanism in humans—a bundle of cells known as the suprachiasmatic nucleus, located at the base of the brain just behind the spot where the optic nerves cross.

Research in this area is exploding. Much of it centers on basic research, including lab-based observations of simple-celled organisms, plants, and mammals. Many of those studying human circadian rhythms are concentrating on the disruptions of these cycles, like those experienced by shift workers, travelers and insomniacs.

In humans, the most common and perhaps the most important consequence of an internal clock gone out of whack is sleep disturbance. But your circadian rhythms are also tied to body temperature, gastrointestinal activity, heart and lung regulation, reproduction and blood cell activity, among other biological systems.

When researchers speak of "setting" the biological clock, they use the word "entraining." Light is the earliest known—and still the most powerful—entrainer for most organisms, including humans. Light appears to regulate the internal clock in two basic ways.

First, light helps keep an organism in line with its 24-hour cycle. Left alone, an organism's internal clock usually gains or loses time. Second, light allows for adaptability. For example, as the sun's light patterns change with the seasons, an organism's biological rhythms will also shift. Some animals make a complete night-to-day shift during winter, for example, to maximize their opportunities to find food, according to William J. Schwartz, M.D., a neurologist at the University of Massachusetts Medical School who studies circadian rhythms in mammals.

In humans, light and lack of light have profound effects. Weak wintertime light is blamed for the depressive condition known as seasonal affective disorder, and irregular and inadequate exposure to light seems to explain, at least in part, a variety of health problems suffered by shift workers. Researchers have found that a bright light of about 2,000 to 3,000 lux (such lamps are available commercially) can be an effective treatment for shift workers, shut-ins and others who don't get enough exposure to light, according to Kathryn Reid, Ph.D., of Northwestern University, who studies the physiological effects of shift work and of various treatments.

Rigorous research is ongoing because we don't yet understand how best to manipulate light. "The judicious use of light and light avoidance is probably the most effective...and is certainly the most well studied remedy for all kinds of problems related to the circadian pacemaker," says Scott Campbell, Ph.D., lead researcher for a Cornell University study. "But none of this has been studied very extensively. Our finding will affect how we treat sleep problems. And sleep is the circadian rhythm that matters most of all."

Several years ago, melatonin was touted as a sleep-inducing, dream-enhancing miracle pill. Sales of melatonin through health food stores and mail order companies are still healthy, and many sellers are adding claims of eternal youth to the mix.

Melatonin is a hormone produced by the pineal gland, at levels that are high at night and low during daytime. There are melatonin receptors in the suprachiasmatic nucleus, and production of melatonin is affected by light patterns and by the circadian cycle. Melatonin acts as a sedative; low doses taken in late afternoon or evening move up the sleep cycle.

While most of the claims pinned to melatonin are probably overblown, it is true that adjusting melatonin levels is one of the best ways to help regulate the biological clock. Melatonin and light adjust circadian rhythms in different ways, suggesting that some internal clock irregularities may require one or the other, or both. People most likely to benefit from melatonin treatment are those who don't get enough exposure to bright light to maintain their normal circadian rhythms (common to shift workers), those suffering from certain sleep disorders, and those subjected to jet lag.

Sleep experts caution that anyone suffering from sleep problems should talk to their health care practitioner, who may recommend testing at a sleep lab. Campbell believes that melatonin's promise is overstated for the average user, although it can be useful for combating jet lag. Fortunately, according to Campbell, melatonin is fairly safe even when it's being misused.

When Campbell calls sleep the "circadian rhythm that matters most of all," he doesn't just mean that sleep disturbances are among the worst consequences of tampering with the body's internal clock. He also believes that sleep research may yet reveal the most important information about circadian rhythms. Sleep—and why we need sleep— is still a deep mystery to biologists. Scientists are looking to genetic research for important clues, Campbell says.

"Circadian rhythms are intimately related to sleep," Campbell said. "We've already seen that there's a very strong genetic component to whether you're an evening or morning person...a napper or a non-napper. The biological clock determines when we're sleepy, but nobody knows why. The next several years will be breakthrough years."

When you travel, your watch can spin through several time zones to match the time at your destination, but it's not that easy to adjust your biological clock. The length of your flight isn't a factor. What matters is the number of time zones you cross. One University of Massachusetts study of baseball teams found that jet lag—and the accompanying impaired performance— appear to be worse for those traveling from west to east.

Jet lag stems from the difficulty our bodies have in adjusting from their usual 24-hour day/night cycle to one that is several hours off. Given enough time, the body would naturally adjust, with the help of cues like light. "The problem is that people go back to their original schedule or go back on the day shift before the natural correction can set it," says Dr. Reid.

Melatonin is still highly touted as a cure for jet lag and is legitimately a biological clock adjuster. It doesn't work well for everyone, however, and research is still trying to clarify how and when it works best.

A comprehensive diet and exercise schedule developed by researchers at the Argonne National Laboratory in Chicago is designed to give your body cues to shift its cycle. See our article about the Argonne plan titled "Say no to jet lag!"

Although the Argonne plan has very detailed instructions for eating, sleeping and light exposure, Cornell's Campbell suggests some simpler guidelines: Pay attention to your exposure to light, which ranks ahead of melatonin as a circadian clock regulator. If you're going to Paris from New York, for example, you will be catapulting yourself six hours ahead of your biological clock. Most flights leave in the evening and arrive in the morning. When you get there, wear dark sunglasses, visit museums and otherwise avoid light as much as possible until the afternoon. Then get as much light exposure as you can.

"Do this for a couple of days," says Campbell. "You're pretty much set."