DNA 'Telomere' Length Tied to Aging, Death Risk

Large study shows association, but doesn't prove cause-and-effect

Thursday, November 8, 2012

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THURSDAY, Nov. 8 (HealthDay News) -- The shorter the DNA sequences found at the end of a person's chromosomes -- known as telomeres -- the higher the risk for death, a large investigation into the microscopic underpinnings of mortality contends.
The finding stems from a fresh look at the role of telomeres, and the degree to which they serve as so-called "biomarkers" of aging.
More than 100,000 participants volunteered both saliva samples and medical records for analysis and review.
The result: Even after accounting for a host of lifestyle factors, shorter-than-average telomere length did seem to be associated with a boost in mortality risk.
"We found that individuals whose telomeres were in the shortest 10 percent were about 23 percent more likely to die in the three years following measurement of their telomeres, when compared with individuals whose telomeres were longer," said lead study author Catherine Schaefer, director of the Kaiser Permanente research program on genes, environment and health, based in Oakland, Calif.
This was true even after adjusting for the effects of smoking, alcohol consumption, education and other factors that are associated with telomere length, the study found.
The findings may suggest that shorter telomere length is not just a byproduct of the aging process but, instead, perhaps itself a significant root cause of aging and death, the researchers said.
A surprise finding was that heavier people had longer telomeres, which contradicts earlier, smaller studies, Schaefer said.
"The higher the body mass index, the longer the person's telomeres," she said. "This was true for both men and women and for all age groups. Other studies have reported that obesity was associated with shorter telomeres."
Schaefer and her colleagues are set to present their team's findings Thursday in San Francisco at the annual meeting of the American Society of Human Genetics.
The authors note that telomeres serve to protect all of the 46 chromosomes found at the human cellular level. And sufficient telomere length is known to be critical in a cell's ability to multiply.
The current effort involved men and women in the northern California region who were enrolled in an ongoing study on genetics and aging. The average age of the participants was 63.
Using saliva samples, the team first set out to genotype 675,000 telomere participant biomarkers. In turn, they cross-analyzed biomarker status with data contained in the electronic medical records, as well as with information from demographic and behavioral surveys that had been conducted two years prior to saliva collection.
The investigators focused on demographic factors that might influence the aging process, as well as lifestyle and behavior factors such as education level, and smoking and drinking habits.
Education levels were linked to longer telomeres while smoking and drinking were linked to shorter telomeres. Depression and other mental disorders did not, however, appear to be similarly linked.
The team determined that shorter telomere length does indeed appear to be associated, on its own, with patient longevity.
In addition, other than during the period of young adulthood, women were found to have longer telomeres than men, the researchers noted. Blacks were also found to have notably longer telomeres relative to other racial/ethnic groups.
The team said more research is needed to see to what degree a patient's prior history of disease and ethnicity might affect telomere status and mortality.
Commenting on the study, Joseph Lee, a human geneticist and associate professor of clinical epidemiology at the Columbia University Mailman School of Public Health in New York City, said that the current effort goes a long way towards validating previous findings.
"Although an association between the shortening of telomeres and mortality has been previously shown, I think this is perhaps the largest ever study of its kind," he noted.
"Now, the question as to whether or not this shortening is an indicator of cellular aging or of some kind of other biological problem is largely debatable," Lee cautioned, "because the shortening of telomeres is also associated with a lot of diseases. Heart disease, Alzheimer's and diabetes, for example. Even mothers with children who have certain disabilities have been shown to, themselves, have shorter telomeres."
All this "makes it really difficult to figure out exactly what's going on, whether telomere length is an independent factor in aging or a consequence," Lee added. "It could, in fact, be both. We're not really sure."
Study author Schaefer acknowledged that "at this time, there are no practical implications of knowing telomere length. Telomere length may help us to better understand the factors that underlie aging, but it cannot predict health or disease with any precision. The health effects of a number of behaviors that are related to telomere length, such as smoking, are well known."
Because this study was presented at a medical meeting, the conclusions should be viewed as preliminary until published in a peer-reviewed journal.
And while the study found an association between telomere length and mortality, it did not prove a cause-and-effect relationship.

SOURCES: Catherine Schaefer, Ph.D., director, research program on genes, environment and health, Kaiser Permanente, Oakland, Calif; Joseph H. Lee, Ph.D., human geneticist, and associate professor of clinical epidemiology, Columbia University Mailman School of Public Health, New York City; Nov. 8, 2012, presentation, American Society of Human Genetics meeting, San Francisco

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