Journal Club

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Short fuse, short telomeres

Men who live a high-stress life—with few social resources, low levels of optimism, and above-average levels of hostility—show signs of the stress in their cells. The ends of their chromosomes, so-called telomeres which wear down naturally as a person ages, are especially short. And their cells are working overtime to produce the enzyme, telomerase, that attempts to correct this wear and tear, researchers report in a new PNAS article.

“We are trying to understand how stress places people at increased health risk,” says Argita Zalli of University College London, first author of the new paper. “Our study suggests that these processes could be mediated through accelerated cellular aging.”

Previous work has shown that psychological stress is associated with shorter telomeres in leukocytes, white blood cells. Zalli and her colleagues wondered how such stress—and a person’s social resources to deal with stress—affected not only telomere length, but levels of telomerase, responsible for keeping telomeres from shortening.

The group recruited more than 500 men and women who were already enrolled in a study on long-term stress and coronary artery disease. Using blood samples, the researchers tested levels of telomerase and telomere length, and then analyzed how the data fit with measures of stress in the subjects.

Men with the combination of short telomeres and high telomerase activity, they found, recovered more slowly from stressful situations—taking longer for blood pressure and stress hormone levels to return to normal, for example. In addition, men in this group were more likely to have poor resources for dealing with stress, adversity during childhood, and a pessimistic view on life. Interestingly, the new study found no association between telomere length, telomerase activity, and stress levels in women. This may be because hormone differences between men and women alter the way the body responds to stress.

“These findings reflect an integration of cellular, systemic, and psychological stress processes,” says Zalli.

The researchers think that long-term psychological stress may make cells in the bone marrow divide more often, wearing down telomeres more quickly since they are shortened with each division. Alternatively or in addition, Zalli says, stress could also make telomerase activity weaker; even with an abundance of the enzyme, the cell is not able to keep telomeres from shortening.

“Everyone responds to stress with activation of various biological pathways and this is healthy—it prepares the person for confronting the challenges they face,” she says. “However, we think that when people have experienced chronic or repeated stress, there is a breakdown in effective mobilization of biological responses.”

The new results don’t tell whether short telomeres and high telomerase activity are associated with health risks or mortality rates, although other studies have linked chronic stress to poor health outcomes. Zalli and her colleagues plan to continue probing the link, and determine whether telomere or telomerase measures can pinpoint populations at risk for certain diseases.

“It would be interesting to see if the links between mental health, psychosocial factors, telomere length and telomerase activity would be the same in a younger age range or among individuals with pre-existing health problems,” says Zalli.

Categories: Medical Sciences | Social Sciences
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