Aging, Cancer and Stress

Elizabeth Blackburn's work on telomeres led to new research and discoveries

Somehow, then, on the road to becoming malignant, cancer cells switch on the telomerase gene before the telomeres become too short for cell division. Surprisingly, the telomeres in cancer cells are often much shorter than the telomeres in the cells of surrounding tissue—evidence that the cancer cells had already begun to replicate (and their telomeres had begun to shorten) at breakneck speed, before the telomerase came back on the scene to perform its vital function.

If telomerase could somehow be inactivated, malignancies would presumably stop before they could spread to other parts of the body, establish new malignancies, and do their extensive damage. (Blackburn suspects, nonetheless, that cancer cells may be able to subvert telomere shrinkage in other ways as well.) Hence, blocking the production of telomerase has become an attractive target for cancer therapies, particularly if they can home in on specific tissue and avoid cells, such as immune cells, that depend on telomerase to keep the body healthy. For the investigators in Blackburn's lab, as well as for geneticists at other universities and within the biotech industry, telomerase blockers have become an important, emerging line of research.

Cancer is by no means the only cell-damager associated with telomere length. In 2004 Blackburn joined forces with Elissa S. Epel, a psychiatrist and clinical colleague at the University of California, San Francisco, to test the role of psychological stress in aging at the cellular level. "We started with the observation [of Epel's] that people look really old and drawn when they have chronic worries and stress in their lives," Blackburn explained. "But we had no hypothesis about whether we'd see an effect on telomeres in the cell. Nobody knew, so I said we should just look."

Blackburn, Epel, and Richard M. Cawthon, a geneticist at the University of Utah in Salt Lake City, conducted a study of thirty-nine women, ages twenty to fifty, who had been caring for a child suffering from a serious chronic illness, such as autism or cerebral palsy. Those women, presumably highly stressed, were compared to a control group of nineteen mothers of healthy children. Stress was quantified in part by the number of years each woman in the test group had been caring for an ill child. That number was combined with other objective measures of stress, including so-called oxidative stress (damage to DNA caused by "free radicals"), one of the major risk factors for cardiovascular disease.

The investigators discovered a clear correlation between the number of years a woman had been caring for her sick child and shortening of telomeres. The stressed women also had lower levels of telomerase in their white blood cells and higher levels of oxidative stress. Moreover, the investigators found that the perceived stress in their test group, as measured by a subjective battery often questions called Cohen's Perceived Stress Scale, was also correlated with shorter telomeres and lower telomerase levels in the blood cells. The finding held whether the mother had an ill child or not. "We didn't expect to see such a clear relationship right across the full range," Blackburn says. "Elissa crafted a beautiful study where she had a well-controlled group of individuals, and the relationship between stress and telomere length really held." In other words, a woman's perception of the level of her own stress is correlated with her body's cellular response. As far as Blackburn and Epel can determine, this result was the first time a mind-body link that reaches into the cell was established.

"Of course, now we want to Understand exactly how stress is affecting the cell," says Blackburn. "Stress is changing hormones in your blood and bathing the cells in something that's different. So that's what we're trying to do in the lab: figure out what things influence telomerase."

Blackburn credits much of her success to supportive research environments and the resulting opportunity to pursue curiosity-driven science. "Thank goodness I don't work in industry," she says. "You can do really good research in industry, but you have to stay on some kind of goal-directed line. [At universities] you're still goal directed, but you can be more creative."

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