Synchronization to a Non-24-Hour Day Reveals Flexibility within the Human Biological Clock

Boston, MA – Researchers from Brigham and Women’s Hospital’s (BWH) Division of Sleep Medicine successfully entrained, or synchronized, individuals to a light/dark cycle that correctly aligned their biological clock to the 24.65-hour day of the planet Mars and to the 23.5-hour day often experienced by astronauts flying in low orbit.

Additionally, the entrainment to the Martian day resulted in long-term changes to the individuals’ circadian period of the biological clock, showing for the first time plasticity of, or flexibility within, this system in humans. These findings have important implications for human space exploration and circadian rhythm sleep disorders, and appear in the August 8, 2007 issue of Public Library of Science ONE.

Circadian rhythm sleep disorders – such as jet lag disorder, shift work disorder and advanced sleep phase disorder – are caused by misalignment between the biological clock and the rest/activity cycle. These can be caused by interindividual differences in circadian periods – a measure of how long it takes to complete one daily cycle.

“Understanding how our biological clock can be adjusted is a critical step in developing therapy for circadian rhythm sleep disorders, which disturb sleep at night and compromise daytime cognitive functioning,” said lead author Frank A. J. L. Scheer, PhD, associate director of the Medical Chronobiology Program at BWH.

In this study, seven healthy young men lived in a personal laboratory room free of time cues for 73 days. Prior to the study, the men maintained a regular 8-hour sleep/16-hour wake schedule for three weeks at home, and did not take medications and/or drugs the week before or during the study.

During the study, ambient light and room temperature were controlled and sleep opportunities were scheduled. Subjects lived on the Martian day and the 23.5-hour day, alternately for two-week intervals. During this time, Scheer and colleagues tested whether the experimental light conditions could synchronize the biological clock of the subjects to the non-24-hour sleep/wake cycles.

Following each two-week session, the researchers tested whether an individual’s circadian period showed longer-term changes that outlived the light/dark cycles – whether the period was lengthened or shortened – by measuring the intrinsic period of rhythms of core body temperature and the hormones melatonin and cortisol.

The researchers found that exposure to moderately bright light for the second or first half of the scheduled wake period was effective for entraining individuals’ biological clocks to the 24.65-hour Martian day or to the 23.5-hour day, respectively.

These results support findings from a related BWH study published in the May 15, 2007 issue of the Proceedings of the National Academy of Sciences; however, the present study extends these findings by showing that participants could be entrained to a non-24-hour day using only about one twentieth the light intensity. Because lower light intensities are sufficient to realign a person’s biological clock than previously shown, less energy would be required to adapt astronauts to a non-24-hour day on the space station – a place under heavy energy constraints.

Furthermore, the researchers found that the circadian period was significantly lengthened following synchronization to the Martian day as compared to the 23.5-hour day, revealing plasticity of the biological clock in humans.

“Most exciting is our finding that the circadian period of the biological clock can be changed,” said Scheer. “This shows that the circadian period is not only determined by one’s genetic makeup, but can be shaped by previous environmental exposure.”

“Because this study reveals, for the first time, that the human brain’s internal clock is capable of long-term adjustment to day length on other plants such as Mars, there’s promise for the development of treatments for folks who have trouble adjusting to the Earth’s 24-hour day,” said senior author Charles A. Czeisler, MD, PhD, chief of the Division of the Sleep Medicine at BWH and Baldino Professor of Sleep Medicine at Harvard Medical School.

Other researchers on this study include Richard E. Kronauer, PhD, of the Harvard-MIT Division of Health Sciences and Technology, and Kenneth P. Wright, Jr., PhD, of the University of Colorado.

This work was supported in part by grants from the National Institute of Neurological Disorders and Stroke, the National Centers for Research Resources, the National Sleep Foundation and the National Space Biomedical Research Institute.