HARVARD GAZETTE ARCHIVES
Human Biological Clock Set Back an Hour
Does not Change with age
By William J. Cromie
The internal clock that drives the daily activities of all living things, from wild flowers to whales, is wound by Earths rotation. The 24-hour cycle, tied to one turn of the planet on its axis, embodies a biological clock mimicked by timepieces invented to measure the human day.
But these external clocks dont exactly match the biological tickings inside ourselves. Many measurements have set the internal clock period closer to 25 hours than 24, a situation blamed for a long list of sleep problems.
Now, the most accurate measurements to date, made by researchers at Harvard University, reveal that our natural daily rhythm is, much closer to that of other living things than previously believed. The better match opens the way for experts to more effectively treat sleep problems involving night work, jet lag, Earth-orbiting astronauts, or just not being able to go to sleep and wake-up when we want.
By recording the daily rhythms of hormones and body temperatures in 24 healthy young and old men and women over a one-month period, the researchers conclude that our internal clocks run on a daily cycle of 24 hours, 11 minutes.
"Thats slightly longer than 24 hours, but significantly shorter than past estimates of 25 hours," says Charles Czeisler, professor of medicine at the Harvard Medical School. "Researchers previously reported a range of 13 to 65 hours, with a median of 25 hours, 12 minutes. The variation between our subjects, with a 95 percent level of confidence, was no more than plus or minus 16 minutes, a remarkably small range."
"These data reveal that the human circadian pacemaker is as stable and precise in measuring time as that of other mammals," notes Richard Kronauer, Gordon McKay Professor of Mechanical Engineering. "These results apply to both young and older people and have practical implications for understanding and developing treatments for sleep disorders tied to circadian (daily) rhythms."
Czeisler, Kronauer, and colleagues report their findings in the June 25 issue of Science magazine. Co-authors of the report include Emery Brown, assistant professor of anesthesia; Derk-Jan Dijk, assistant professor of medicine, and research fellow Jeanne Duffy, all of the Harvard Medical School.
"It was both surprising and reassuring that the human clock runs with the same precision as that of other living things," Czeisler comments. "But we did not expect to find that both young and old people have the same daily period."
Many experts believe that the clock speeds up with age, and they use that idea to explain why elders wake-up earlier in the morning. With that idea now put to sleep, researchers need to come up with new theories for these early awakenings.
Why are these measurements more accurate than previous ones?
"Other investigators used elaborate procedures to shield subjects from time cues and the outside world," answers Czeisler, who is also director of circadian and sleep disorders medicine at Brigham and Womens Hospital in Boston. "They even coiled copper wire around the rooms in which people were isolated to counteract natural electromagnetic fields. However, these experimenters allowed their subjects to switch on lights when they were awake and turn them off when they wanted to sleep. They didnt think this would have any effect, but switching on electric lights resets the biological clock. Its the same as resetting your watch."
Kronauer calculated that changing ordinary room light in such experiments can shift the apparent circadian cycle by more than 40 minutes.
The Harvard team had their subjects go to bed four hours later each day, effectively creating a 28-hour day. This strategy disconnected the biological pacemaker from clock time.
"The 28-hour cycle distributed light exposure, sleep and wakefulness, work and play evenly around the biological clock," explains Czeisler. "The men and women did not get light exposure at the same time each clock day. Instead, they experienced a six-day week in which light and dark occurred at different times each day."
This altered schedule freed their internal clocks from the sleep-wake cycle and allowed them to tick at the natural period. Despite six-day weeks, their body temperatures and hormone secretions went through seven cycles every week. Sleepiness was tied to a drop in core body temperature and to an increase in melatonin, a hormone secreted by the pineal gland and sold over-the-counter as a sleeping pill.
Czeislers crew also measured changes in cortisol, a hormone involved in metabolism and other basic body functions. Cortisol naturally drops to its lowest levels at bedtime and reaches its highest point during early waking hours.
The result was clear. No matter when the subjects went to bed or got up, and whatever they did while awake, body temperature and hormones rose and fell on an average cycle of 24 hours and 11 minutes.
What do people do when isolated in a timeless room for a month? Some of them were graduate students, and they worked on various school projects or wrote their dissertations. Others did oil paintings or busied themselves with jigsaw puzzles. One man, a geologist, brought his rock collection and chipped the time away with a rock hammer. Yet others read, thought about the world, and enjoyed the phoneless, e-mailless solitude.
Re-thinking Biological Time
Czeisler, Kronauer, and some colleagues first presented the case for a near 24-hour biological clock in 1989. "The many years of experiments done since then, including this latest work, makes us confident in the accuracy of our measurements," Czeisler says.
Apparently, Earths rotation impresses a 24-hour period on the genes of humans and other living things. The human clock consists of a cluster of nerve cells (the suprachiasmtic nucleus) barely a hundredth of an inch in size, located deep in the brain and connected to the eyes optic nerves.
"Accepting the near 24-hour period means that all the ideas about daily human rhythms that we take for granted must be rethought," Czeisler says. For example, biological-clock lore states that we drift to a later wake-up hour on weekends because we fail to reset the 25-hour cycle each morning as we go to work.
"Were not drifting," Czeisler insists. "Were pushing ourselves to a later time with our exposure to electric lights from sunset to bedtime. That resets our biological clocks."
The resetting, which leads to difficulty in awakening on Monday, can, in many cases, be "cured" by going to bed earlier on weekends. Awakening too early often can be avoided by going to bed later.
To deal with night-shift work, jet lag, sleeping in an orbiting spacecraft, or the winter blues, our biological clocks can be reset by timed exposure to bright light. "To determine the correct exposure, however, we must pin down the internal circadian period, the natural rhythm of our bodies," Czeisler points out. "Now, we are able to do this more effectively than before."
Copyright 1999 President and Fellows of Harvard College