http://www.eurekalert.org/pub_releases/2001-08/wuis-sar081301.php

Sleepless aged rats show biological clock problems

One of the problems of the aged is getting a good night’s sleep. Often, the
elderly sleep fitfully through the night only to be overcome by drowsiness
during the day and nodding off then. A general feeling of tiredness and
irritability goes hand-in-hand with this condition. Now a biologist at
Washington University in St. Louis and colleagues from France and the
University of Virginia have found this problem may be traced to a faulty
biological clock — at least in aged rats.

Erik Herzog, Ph.D., assistant professor of biology at Washington
University, examined cells involved in the generation of circadian rhythms
— the 24-hour cycles in things like alertness and hormone levels. In
collaboration with Fabienne Aujard, D.V.M., Ph.D., of France’s Centre
National de la Recherche Scientifique, and Gene Block, Ph.D., professor of
biology at the University of Virginia, Herzog found that the electrical
activity of the clock cells in aged rats was not regular compared with that
of young and middle-aged rats.

"In the case of the aged rats, many of them showed fragmented behavioral
rhythms," Herzog explained. "They were still rhythmic, but showed bouts of
activity when the rats normally would have rested and inactivity when the
young animals were active. "So, the rats, like elderly humans, took naps
when they would have normally been active. Remarkably, the cells in their
biological clock reflected this behavior."

The research is supported by the National Institutes of Health and will be
published in the forthcoming issue of Neuroscience. Herzog cannot surmise
exactly what role aging is playing in this irregularity, but he doesn’t
think it’s a result of the circadian rhythm network breaking down.

"The deterioration of rhythmicity would appear to be a single cell
property," he said. "The individual pacemaker cells appear to be losing
their ability to mark time. We could argue that this is evidence of aging
acting at the level of single cells."

The hub of circadian rhythm in rats and humans and other mammals is found
in the suprachiasmatic nucleus (SCN), a part of the hypothalamus that can
be found on the bottom of the brain just above the roof of your mouth where
your optic nerves cross. There are roughly 10,000 cells in this nucleus.
The timekeeping mechanism in these cells depends on daily cycles in gene
activity. The first of these genes identified in mammals was called CLOCK,
for "circadian locomotor output cycles kaput."

The first thing that Herzog and his collaborators have established in
studying this region is that SCN neurons can act as autonomous pacemakers,
keeping time without input from other cells. While the SCN is required for
circadian rhythmicity, there are other circadian oscillators in the body
and in different parts of the brain. However, without the SCN, other
circadian rhythms disappear. Herzog and his colleagues study rat SCN cells
in vitro — outside the body — and hope to gain knowledge of how these cells
normally work and what happens in cases of jet lag, shift work, blindness,
fever, aging and other conditions that appear to alter our daily schedules.

"We think that there is a master clock in the SCN, and many ‘slave’ clocks
in the brain and body," Herzog said. "The ‘slave’ clocks may receive daily
synchronizing signals from the master, but when they get out of phase, it
takes several days to catch up. That very well may be happening with jet
lag. It’s not the SCN that gets out of whack in a different environment –
for instance, after flying to Paris – but other structures inside and
outside of the brain."

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