The Ravages Of Stress

By MICHAEL D. LEMONICK

Everyone knows that stress can make you age before your time--but everyone knows is folk wisdom, not science. What science has established so far is that people under chronic stress tend to have weak immune systems and run an elevated risk of cardiovascular disease. But that doesn't necessarily prove that stressed-out people are actually aging prematurely, even if they look older than their years.

But an important new study shows that folk wisdom and subjective judgment may, in this case, be right. Writing in last week's Proceedings of the National Academy of Sciences, a team of scientists reported that long-term, unrelenting stress on mothers can damage the DNA of their immune-system cells in a way that may speed up the aging process. "It's an immensely exciting result," says Robert Sapolsky, a Stanford University cell biologist who wrote a commentary accompanying the report.

The study began when Elissa Epel, a psychologist at the University of California, San Francisco, asked her colleague Elizabeth Blackburn, a biochemist, whether anyone really knew why people under stress look haggard and old. "I told her, 'Nobody has any idea,'" recalls Blackburn. "And then I said, 'Let's have a look.'" They gathered a team of psychologists and biologists and recruited 58 women ranging in age from 20 to 50. Thirty-nine of the women were the primary caregivers for a child chronically ill with cerebral palsy, autism or some other serious disorder; the rest had healthy kids. The researchers gave all the mothers a standard test that measured how stressed out they had been feeling during the previous month. Then they drew blood and examined peripheral blood mononuclear cells, part of the body's immune system.

Even after the scientists corrected for factors such as age and body-mass index, those crucial cells looked different--in three important ways--in the women who reported the highest stress levels. First, the cells had shorter telomeres--bits of DNA that cap the ends of chromosomes. In lab experiments, scientists have shown that telomeres get a bit smaller every time a cell divides, and that when telomeres are worn out, cells can't divide anymore and ultimately die. In humans, older people tend to have shorter telomeres--and by this measure, the most stressed women in the study had cells that looked 10 years older than their chronological age. It's not an open-and-shut case that telomere shortening is the key to aging, says Sapolsky, "but it's the best candidate we have. It may be one of many factors, but it may well be the most important."

The most stressed women also had lower levels of telomerase, an enzyme that repairs damaged telomeres. Again, reduced telomerase isn't necessarily the key to premature aging, but people with a rare genetic condition that reduces their telomerase production tend to show outward signs of premature aging and often die young of heart disease and weakened infection resistance.

Finally, the stressed women's cells had higher levels of free radicals, a type of highly reactive molecule that can damage DNA. One might argue that women whose children were born with those disorders already had something wrong with their DNA and that stress wasn't the cause. But that wouldn't explain another crucial fact: the degree of cellular damage was highest in women who had been caring for a disabled child the longest. "We tried our hardest to make the result go away," says Blackburn, "because we wanted to make sure we weren't fooling ourselves. But we couldn't."

The experiment will have to be replicated before it's fully accepted, and the prospect of some sort of antiaging medicine to protect cells is distant at best. Still, the study seems to tie together a lot of interesting threads. "What will really be interesting," says Sapolsky, "will be to trace the pathways--how you go from the level of people getting no sleep down to the cellular level. It will be amazing once we understand that."