Stressed to death: mental tension ages cells.

A new study puts evidence behind the old adage that stressful experiences can give a person gray hairs. Scientific data now indicate that prolonged psychological stress might cause a person's cells to age, and possibly die, significantly faster than normal.

Previous research had shown that protein-DNA complexes called telomeres serve as a cell's timekeeper, telling it how long to live. Telomeres protect the ends of chromosomes, much as plastic tips protect shoelaces. Each time a cell divides, enzymes chew off a tiny portion of its telomeres. When the caps are whittled down to nubs, cells cease dividing and soon die.

Scientists have long known that stress can harm a person's health by, for instance, lowering immunity or raising blood pressure. "We wanted to look at some of the molecular underpinnings of why that might be true. No one actually has clear ideas," says Elizabeth Blackburn of the University of California, San Francisco.

Blackburn and her colleagues examined whether telomeres might play a role. Her team recruited 58 healthy women between the ages of 20 and 50. While all the women were mothers of at least one child, 39 members of the group were primary caregivers for a child who was chronically ill with a disease such as cerebral palsy.

Each volunteer answered a questionnaire on how much day-to-day stress she perceived in her life. Not surprisingly, mothers with chronically ill children generally reported more stress than did women with healthy children.

Blackburn's team measured telomere lengths in immune cells called mononucleocytes collected from blood samples of each volunteer. The researchers also assessed the activity of an enzyme called telomerase, which maintains telomeres.

"There was a very striking connection" between stress and telomere length, Blackburn reports. Mothers who perceived their stress levels as high had significantly shorter telomeres and less telomerase activity than did women reporting lower stress. From the telomere lengths, the researchers estimate that cells from the highly stressed women resembled cells of low-stressed volunteers who were 10 years older.

The researchers aren't sure how stress affects telomere length and telomerase activity, but they speculate that chemicals known as free radicals might impede telomerase function. Further tests showed that women who reported higher stress also had more free radical damage to their cells than women under less psychological strain did.

The findings, to be published in an upcoming Proceedings of the National Academy of Sciences, are "very provocative, in the best sense of the word,' says Robert Sapolsky, a biologist at Stanford University. "This is very exciting because it ties in stress to, arguably, the best cellular pacemaker of aging out there."

Blackburn's results "make sense," says Fred Goldman, a pediatric oncologist who studies telomere biology at the University of Iowa in Iowa City. "We know that people who are stressed out look haggard.... If we have less stress in our lives, we might live longer."