Stress Can Accelerate Brain’s Aging, Researchers Find : Neurology: Studies with rats show that prolonged exposure to strain can release hormones that damage cells important to learning and memory.

That high-stress job may be doing you more harm than you thought.

For the first time, researchers have found direct evidence that prolonged exposure to stress in rats can accelerate the aging of brain cells and lead to impairment of learning and memory.

In the studies, stress caused rats to produce abnormally high levels of stress hormones, such as adrenaline, which damaged brain cells, a Kentucky researcher reported Monday in the Journal of Neuroscience.

In older rats, the stress led to the death of brain cells, a finding that may shed light on the cause of Alzheimer’s disease--which already has been correlated with high levels of the hormones.

The new study “represents an important advance in research on biomarkers of brain aging and may ultimately point the way to interventions that will prevent (deterioration of mental processes) in older people,” said neurologist T. Franklin Williams, director of the National Institute on Aging, who is familiar with the new study.

“In my judgment, the discovery plays a key role in tying together many disparate observations from different laboratories that study aging,” said neurobiologist Zevan Khachaturian, also of the institute. Research on the stress hormones, he said, “is getting more and more exciting.”

The results are important because the region of the brain that the researchers studied is the hippocampus, the same region that is severely damaged in humans suffering from Alzheimer’s, a devastating progressive disorder that affects at least 2 million Americans, most of them over 65.

Khachaturian said that it remains unclear whether the phenomenon observed in the rats also takes place in humans.

“We would conjecture that (it) would . . . but that will be very difficult to prove” because researchers cannot ethically submit humans to the same types of studies performed on rats. To get around that problem, researchers are now studying autopsied human brains to look for the effects of stress.

The new study suggests that stress makes brain cells in the hippocampus--which is important to learning and memory--work harder and thus leaves them more vulnerable to damage from other causes, in much the same way that fatigue and exhaustion can render an individual more susceptible to colds and flu, Khachaturian said. The damage to hippocampal cells might be caused by a short interruption of blood flow to the brain, low blood sugar levels, chemicals in the environment or chemicals produced by the brain, the researchers said.

The hormones involved in the new study include adrenaline and cortisol, both of which are released into the bloodstream by the adrenal glands as part of the “fight or flight” response to stress. These hormones help the body cope with stress by making energy-containing molecules more available to the nervous system and heart.

Prolonged exposure to the hormones has previously been linked to high blood pressure, osteoporosis, coronary artery disease and perhaps cancer. Neuroscientist Philip W. Landfield of the University of Kentucky, the primary author of the new paper, has been working for 12 years to tie such exposure to mental deterioration. “In the beginning, he was a lone voice in the wilderness,” said Khachaturian, “but now others are picking up on it.”

Previous studies by Landfield and others have indirectly linked the stress hormones to mental deterioration. Neurologists Bruce McEwen of Rockefeller University in New York City and Robert Sapolsky of Stanford University have shown that injections of the hormones into the brains of rodents cause mental deterioration.

Landfield has shown that removal of the adrenal glands at a young age reduces age-related degeneration of hippocampal cells in the animals. The “missing link,” Khachaturian said, was the demonstration that stress would cause the same effects as injections of the hormones.

To study this, Landfield, working with researchers at Bowman Gray School of Medicine in Winston-Salem, N.C., subjected rats of different ages to a test in which they had to shuttle from one side of a plastic runway to the other to escape a mild electrical shock. Because the harmless shocks were given randomly in four-hour sessions, the rats were exposed to the stress of not knowing when they would occur.

After six months of such stress five days a week, followed by a three-week recovery period, Landfield and his colleagues studied electrical activity between cells and the hippocampus and found that it was significantly reduced. That reduction had previously been shown to cause impaired learning and memory in rats.

Previous studies had shown that such stress significantly increases the rats’ levels of stress hormones.

When the group autopsied the rats, they also found that older rats exposed to the stress had lost twice as many hippocampal cells as elderly rats who were not stressed--50% of the cells for the stressed rats compared to 25% for normal rats.

“This indicates that the aged brain is much more vulnerable than the young brain to the neurodegenerative effects of stress hormones,” Landfield said.