The Tale of the Telomeres Gets Ever-More Complex

Your destiny may be written, not in the stars, but in the telomeres that cap the ends of your chromosomes.

And your telomeres’ fate in turn may be influenced by your mental health.

This fascinating saga is becoming even more intriguing as it plays out.

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In 1965, scientists reported that the older a person is, the fewer times his or her cells divide when cultured in the lab. In 1990, they reported that each time a human cell divides in the lab culture, the telomeres shorten a bit, until they get so short that the cell is unable to divide further and dies.

In 2006, Naomi Simon, M.D., an associate professor of psychiatry at Harvard Medical School, and colleagues found that individuals with mood disorders have shorter telomeres than do healthy control subjects (Psychiatric News, June 2, 2006). Last year, scientists found that children who had been institutionalized had shorter telomeres than children who had not (Psychiatric News, July 1, 2011) and that hostility can chip away at people’s telomere length (Psychiatric News, December 16, 2011).

And now Lawrence Honig, M.D., Ph.D., a professor of clinical neurology at Columbia University, and his colleagues have found that telomere length may predict death in older people. The results appeared online July 28 in the Archives of Neurology.

The cohort that Honig and his team studied included 1,978 individuals who ranged in age from 66 to 101, with an average age of 78. The sample was also multiethnic—mostly African American, Hispanic, and non-Hispanic white.

The scientists drew blood from the subjects during a baseline visit, extracted white-cell DNA, and then determined the length of the telomeres within the DNA. The scientists followed the subjects for an average of eight years. They then assessed whether telomere length predicted mortality, taking age, gender, ethnicity, education, APOEe4 carrier status, and dementia into consideration.

They found that telomere length predicted remaining lifespan. That is, telomeres were significantly shorter in those who subsequently died in the follow-up period than in those who survived.

Why this is the case isn’t clear, they acknowledged. It could be that truncated telomeres lead to disease and death. “Evidence from cell culture and from animal models suggests that very short telomeres are themselves deleterious, increasing errors in the cell division process and possibly the development of cancer,” they noted. Or it could be that some environmental or genetic influences are both shortening telomeres and causing death.

Gender Differences Discovered

The scientists also made two other key findings. One was that telomeres were significantly shorter in male subjects than in female ones. The other one was that while telomeres were generally shorter in subjects who were older, there were wide variations in telomere length among people of a comparable chronological age. “Indeed, the variation between individuals within age groups is larger than the effect of many years of aging,” they said. And the reasons for such variation appear to lie in findings obtained by other researchers.

Specifically, evidence suggests that telomere length is a heritable characteristic, with varying estimates of heritability as high as 80 percent. But that leaves some 20 percent of the length to be determined by the environment, and both negative and positive environmental factors seem to have an impact on it.

The negative factors are things such as childhood adversity, mood disorders, and hostility. The positive factors are things such as a good diet and exercise. Telomeres even appear capable of growing longer, depending on the individual and the environment.

Clinical Implications Cited

The new findings have implications for various clinicians, including psychiatrists, but the “implications depend upon whether telomeres are a marker of biological aging or a causative factor in the pathway of biological aging,” Honig told Psychiatric News. “If the former, then it is possible that telomere length might help us monitor the aging process. If the latter, then intervening in the telomere maintenance pathway might help alleviate some of the features of aging.”

He and his colleagues will now be looking at “what changes there are in telomere length longitudinally,” Honig said. “And we are very actively looking for genes that might influence telomere length….”

These data “continue to support the hypothesis that telomere length is a marker of aging,” Simon told Psychiatric News. “As the authors note, however, there was more variability in telomere length among individuals within the same age cohort than change in telomere length over time, suggesting that much of telomere length is determined by other factors such as genetics, and, as they found, gender.”

“More research,” she continued, “is needed to understand the underlying biology of the telomere length–aging relationship, what factors may influence changes in telomere length over time, and whether interventions to reduce the rate of telomere length shortening in individuals would have health benefits or not, as telomere biology is complex and intricately involved in cancer development as well.”

The study was funded by the National Institutes of Health, the Alzheimer’s Association, the Henry P. Panasci Fund, and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain.

An abstract of “Association of Shorter Leukocyte Telomere Repeat Length With Dementia and Mortality” is posted at http://archneur.jamanetwork.com/article.aspx?articleid=1217317.