Aging, Neurodegeneration Reset the Brain’s Internal Clock

by Kayt Sukel

July 9, 2012

As we age, sleep can become much more elusive. Elderly people often have difficulty both sleeping through the night and staying awake during the day. While sleep issues have often been linked to myriad health problems, new research by scientists at the Leiden University Medical Center in the Netherlands suggests that changes to neural activity in the suprachiasmatic nucleus (SCN), an area of the brain that houses the internal clock, may underlie this age-related shift in sleep and wake patterns—and provide new methods for treatment.

Common sleep issues in the elderly

My 93-year-old grandmother has great difficulty sleeping through the night. She has trouble falling asleep and wakes often once she does. As a result, you can usually find her periodically snoozing throughout the day—and watching television late into the night. Gayatri Devi, a neurologist at the New York University School of Medicine, says this is very common in the elderly. Normal aging results in changes to sleep architecture, including shallower sleep stages and more frequent awakenings. But this change in architecture is often exacerbated by other health issues and lifestyle choices.

“As people age, they can have deterioration in their health that can result in problems with sleep. Some of the most common are prostrate problems or urinary problems. People are waking up often to go to the bathroom and that interferes with overall sleep quality,” she says. “Others may have poor sleep hygiene. They may be used to working late and getting up early and now that they are retired they take a lot of daytime naps, watch television late at night or take drugs, which can aggravate sleep problems.”

Generally, physicians treat sleep issues, in the young and old alike, with drugs like Ambien or benzodiazepine—medications that are indicated for short-term use but are often used beyond that. “Over time, it promotes dependence on these medications on sleep, resulting in the inability to go into a natural sleep on your own,” Devi says. “It’s a big problem.”

A disrupted network

Studying the changes to sleep architecture may not only provide better understanding of age-related brain changes but ultimately provide safer, more effective treatments for sleep disturbances. Johanna Meijer, a researcher at the Leiden University Medical Center in the Netherlands, and her colleagues found that changes in SCN neurons may explain how and why sleep patterns change over time.

Neurons in the SCN are responsible for our sleep/wake patterns, becoming active during the day and silent at night, communicating circadian rhythms to the rest of the body. “In young, healthy subjects, clock cells show a peak in the activity during the day and then show a drop in activity at night,” she says. “The cells are very nicely lined up and closely in phase. This renders a very strong and powerful rhythm. But in older tissue, we see a secondary group of cells that become active at the wrong time of the cycle, decreasing the overall signal.”

In a study published in the April 25 issue of Journal of Neuroscience, Meijer’s group recorded activity in the SCN cells and found that damage to the individual cells was much more severe than that observed across the network, a huge shift from the way scientists previously characterized changes to sleep architecture. They also identified age-related changes to the SCN cell membranes that might account for the observed damage.

“This is an example of just how important cellular networks are,” she says. “We were not surprised to see the amplitude of the rhythm decreased at the network level. But we were, in fact, very surprised to see that the damage at the single-cell level was so much more severe than at the network level. There were almost no rhythms left in some cells—the effect of aging was very pronounced. Yet the network was able to compensate a bit for those deficiencies and still develop a reasonable rhythm.”

Neurodegeneration and the SCN

Age is not the only factor that can affect SCN cells. Christopher Colwel at the University of California Los Angeles Medical School, has found that neurodegenerative disorders are also linked to a disruption in SCN neural activity. In a study published in the November 2011 issue of Experimental Neurology, his lab examined circadian rhythms in a mouse model of Parkinson’s disease. The found that SCN neurons fired less during the day, changing sleep/wake patterns.

“Diseases like Huntington’s disease and Parkinson’s disease are characterized clinically by their motor symptoms,” he says. “But recent data has shown that there is a big disruption in the sleep-wake cycle, and this disruption is occurring maybe even a decade before the onset of those motor symptoms.”

Colwell argues that this raises the possibility that symptoms common to neurodegenerative disease and normal aging may be aggravated or even caused by years and years of sleep problems.

“If you disrupt the sleep/wake cycle even in a young healthy person, you see changes to the nervous system. You see problems with regulation of glucose and cardiovascular problems,” he says. “So this is a very promising therapeutic angle. If we can treat and deal with sleep/wake disturbances early on, we may have a chance of not only improving the quality of life for these patients but also delaying or preventing the onset of some of these other diseases and symptoms.”

A promise of treatment

While some have argued that understanding the mechanisms underlying the changes to SCN neuron activity may present new drug targets, Meijer and Colwell agree that people may be better served by making some relatively easy changes to their daily habits to improve sleep.

“Currently, sleep problems are usually treated with drugs. But I would say that the elderly should expose themselves to sufficient light levels during the day and try to be active with mild levels of exercise. These things are enough to activate the clock’s network,” says Meijer.

Preliminary data suggests that the times of day you eat and exercise may also help keep the internal clock in sync. “We know that exercise is good but we think that when you exercise is a big influence on maintaining the function of your sleep system. The same exercise that is beneficial to sleep when you do it in the morning may actually be disruptive to the sleep-wake cycle if you do it at night,” says Colwell. Late night eating may also result in problems. 

But Meijer says these changes should not be limited to just older individuals. Younger people can also benefit by picking up good sleep habits early. “Students live lives that work very much against their clocks by staying up late at night and sleeping in too late in the morning,” she says. “By living a more regular life, they can help get your circadian clock back into its proper rhythm and help avoid insomnia.”