Can Stress Reduction Fight Some Signs of Aging?

Psychological stress has long been thought to contribute to premature aging. Now one of the pathways in this association may have been identified. It is premature acceleration of the telomere shortening process.

The finding comes from a study published in the November 30, 2004, Proceedings of the National Academy of Sciences. The major investigator was Elissa Epel, Ph.D., an assistant professor of psychiatry in the University of California at San Francisco's Health Psychology Program.

Telomeres are DNA-protein complexes that cap the end of chromosomes within a cell. Each time a cell divides, the telomeres within it shrink a little, until after numerous rounds of division there is so little telomere material left that the cell can no longer divide. Telomere shortening is part of the normal chronological aging process. The rate of shortening accelerates once an individual reaches 50 or 60.

The question that Epel and her coworkers investigated was whether psychological stress hastens the telomere-shortening process that occurs with normal chronological aging. They selected as their subjects 39 healthy women between the ages of 20 and 50 who were mothers of a chronically ill child and 19 healthy women in the same age range who were mothers of a healthy child. They expected that the former subjects felt more psychologically stressed than the latter, which psychological testing generally confirmed.

The researchers then took samples of peripheral blood mononuclear cells from each subject and measured the length of the telomeres in the cells. They found that psychological stress was significantly associated with shorter telomeres, even when possibly confounding factors such as chronological age, body mass, smoking, and vitamin use were considered. In fact, the 14 women with the highest levels of perceived stress had telomeres shorter on average by the equivalent of at least one decade of additional aging compared with the 14 women with the lowest levels.

Moreover, the 14 subjects who had rated themselves as being the most stressed psychologically were found to have significantly lower telomerase activity and higher oxidative stress in their cells than the 14 subjects who had rated themselves as least psychologically stressed. Telomerase is an enzyme that helps protect telomeres from outside insults, and oxidative stress can hasten the shortening of telomeres.

And within the caregiver group, the longer the subjects had cared for a chronically ill child (anywhere from one to 12 years), the shorter their telomere length, the lower their telomerase activity, and the higher their oxidative stress were even after controlling for age.

“Since we hypothesized that psychological stress may eventually affect telomere length, the results should not have surprised us,” Epel said in an interview. “But thinking that a relationship is feasible conceptually was actually very different from seeing it `live' in the data. I was quite taken back to realize that stress indeed had effects visible at the intracellular level—at least in this study. I get excited by data intellectually, but seeing [these] actually made my heart race.

“[In other words] when linking two factors that are so distant from each other in terms of level of analysis—cognition versus molecular structure of DNA segment—one would expect weak and ambiguous results. [Yet] the consistent pattern of findings made us confident that we were not seeing some random pattern that just happened to come out. Telomere length, telomerease activity, and oxidative stress were all related to life stress....

Owen Wolkowitz, M.D., a professor of psychiatry at the University of California at San Francisco, told Psychiatric News, “This is a landmark study in many ways, and one that will revolutionize how we think about the mind-body connection. It links psychological `stress' with basic physiological processes of cellular aging and DNA damage. Demonstrating a causal connection between these variables (which will require longitudinal studies) would offer up one of the `holy grails' of healthy psychology and stress physiology, namely, the basic mechanisms by which psychological life stress contributes to physical illness and aging.

The study was funded by the MacArthur Foundation, the Hellman Family Fund, the Kirsch Foundation, the Burroughs Wellcome Fund, the Dana Foundation, and the National Institutes of Health.

The study, “Accelerated Telomere Shortening in Response to Life Stress,” is posted online at<www.pnas.org/cgi/doi/10.1073/pnas.0407162101>.▪