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University of Basel

The 25-hour man

Text: Oliver Klaffke

Each person’s wake-sleep rhythm is calibrated at 24 hours. In Basel, scientists are studying a man for whom the mechanism does not work. This is providing them with new insights into human chronobiology.

There was huge excitement when around 15 years a¨¨go special receptors in the retina whose job is to measure light levels were discovered,” says sleep researcher Christian Cajochen. “They transmit information to the brain about whether it is day or night.” The existence of a third kind of receptor, besides the well-known rods and cones that allow us to perceive colors and tones, is of huge significance for chronobiology. These receptors – photosensitive ganglion cells – explain how a person’s internal clock is tuned into the daily rhythm of their environment.

The importance of the mechanism becomes clear when this synchronization does not work, as in the case of a man whom Cajochen’s colleague, Dr Corrado Garbazza, is studying.

Every person has their own sleep-wake rhythm, which runs for about 24 hours. It is synchronized with their environment by the change in light levels over the day-night cycle, which is picked up by all the photoreceptors, as well as by the photosensitive ganglion cells in the eye, and transmitted to the brain – specifically, to a region of the hypothalamus called the suprachiasmatic nucleus. This has its own dynamic. It is the location of the internal clock, so to speak, and works like a pacemaker – in other words, it generates the circadian rhythms. The temporal rhythms of all the cells in the body are synchronized from here. “Every cell has its own clock, which operates independently and continually has to be reset to the right time by the control center in the brain, like a radio-controlled clock,” Cajochen says. This control center, the suprachiasmatic nucleus, is supplied with information about changing light levels over the course of the day via the photosensitive ganglions. In nearly all people, the system works so well, thanks to this fine-tuning, that they do not notice its effects, unless they travel overseas and suffer jetlag or they are involved in shift working.

Inability to synchronize

The man Garbazza is studying cannot synchronize his sleep-wake rhythm with his surroundings. At 25.27 hours, his rhythm is significantly longer than the 24-hour day, meaning that his sleeping and waking phases move around over time. The researchers call him the “non-24-hour man”. If he travels to another time zone, his rhythm does not adjust to the new conditions but runs on independently. Back in Switzerland, too, his sleep-wake rhythm remains unchanged. Every day he gets tired a bit later and gets up a bit later; on average, the difference is about 1.27 hours a day. Obviously this makes it difficult for him to cope with a normal work pattern that requires him to turn up at the office at the same time every day.

The man’s case was so unusual that initially the Basel researchers assumed that, rather than being due to an inability to synchronize with the environment, it must have other causes. Garbazza recorded the man’s sleep-wake rhythm continuously for more than six months, determined his melatonin profile every month and analyzed the circadian gene expression in his fibroblasts. In the process, it became clear that these measurements were “running free” on a 25.27-hour cycle, and thus were not synchronized with the 24-hour day.

One of the scientists’ working hypotheses – that they were dealing with an acquired behavior – was thereby disproved. For the researchers, this was clear evidence that the man’s inability to synchronize his sleep rhythm had a physiological component. In the case of the “non-24-hour man”, although the cells are synchronized centrally within the body, the circadian rhythm continues stubbornly to follow the time set by the internal clock. This happens because the mechanism for synchronizing it with the man’s environment, according to changing light levels, does not work. That is very unusual in those with normal vision, but it is relatively common in people who are totally blind.

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