Years weaken signal of body’s master clock

By Fariss Samarrai

Imagine a wall full of clocks with a large dominant clock controlling the synchronization of the peripheral clocks. Now imagine the big clock con-
tinuing to keep time, but, as time goes on, its connecting signal to the smaller clocks weakens. Some of the smaller clocks eventually become desynchronized and some stop running.

This weakening of the signal, rather than a problem with the central timekeeper itself, apparently is the cause of alterations in the biological timing system in aging mammals – possibly including humans — according to a new U.Va. study in the current issue of the Proceedings of the National Academy of Sciences.

This may explain why older people experience sleep disorders — the signal from the master clock in the brain has weakened, even as it keeps on ticking. This weakened output causes some of the peripheral clocks in other organs to eventually stop oscillating or to fall out of proper synch, causing sleep disruption and malaise.

Lack of sleep can affect more than a person’s level of alertness. In the long term it can disrupt the body’s metabolism, affect eating cycles, lead to declining cognitive abilities and possibly a shortened lifespan. Sleep disorders also are associated with Alzheimer’s disease.

“Previous studies in our laboratory revealed that the electrical signal from neurons in the brain’s master clock is weaker in older animals, which led us initially to believe that the central clock mechanism deteriorates with age,” said Gene D. Block, professor of biology and one of the study’s lead researchers.

“Our new finding demonstrates that the molecular machinery of the master clock continues to function normally. Taken together with our earlier studies, this suggests that there may be an age-related failure of the conversion of the clock’s molecular rhythm into the electrical or humoral signals that the brain uses for communication. These weakened central signals may fail to keep some peripheral clocks appropriately synchronized or, in some cases, even rhythmic.”

The scientists studied tissue from the brain and other organs of older mice and measured the activity of a gene that is part of the biological clock. They found that the central clock in the brain, the suprachiasmatic nucleus, maintained proper periodicity and synchronization. Clocks in some peripheral organs, such as the liver and kidney of older animals, were either improperly synchronized or had lost rhythm entirely.

“This new knowledge could eventually lead to new therapies for age-related desynchronization,” said Block, who is also U.Va.’s vice president and provost. “Arrhythmic or improperly synchronized tissues of old animals could possibly be stimulated by a treatment to oscillate normally.”

U.Va. researchers who conducted the study include lead scientist Shin Tamazaki, Block, Michael Menaker and Martin Straume. Hajimi Tai and Y. Sakaki of the University of Tokyo also contributed.