Chromosomes Shorten With Age, Predict Mortality

EMBARGOED BY THE LANCET UNTIL 6:30 (EST) January 30

As if it's not bad enough that people lose their hair, teeth, and eyesight as they age, their chromosomes desert them, too.

As people get older, telomeres--the ends of chromosomes--get shorter in all dividing cells in the body, except the germline (cells from which a new organism can develop). This, according to University of Utah medical researchers, holds major health implications for people over age 60 because shortened telomeres in blood are associated with increased risks of dying from heart disease or infectious diseases.

In a study published in the February 1 issue of the international medical journal, The Lancet, researchers from the U of U School of Medicine's Department of Human Genetics, Huntsman Cancer Institute, and Department of Family and Consumer Studies concluded that women and men with shorter telomeres died sooner than people with longer telomeres. Women with shorter telomeres died a median 4.8 years sooner, while men died a median 4 years earlier than their counterparts.

"Telomere length was a significant predictor of mortality in people ages 60 to 74," said Richard M. Cawthon, M.D., Ph.D., research assistant professor of human genetics and lead author of the study.

In people age 75 and older, telomere length was a moderate predictor of mortality.

The researchers studied 143 unrelated Utah residents, ages 60 to 97, who donated blood from 1982-1986. At the time the study concluded, 101 of the people had died.

People whose telomere length was in the bottom half of the study group had a heart disease mortality rate more than three times higher than subjects whose telomere length was in the top half, the researchers found.

Those with telomere length in the bottom quarter had an infectious disease mortality rate eight times higher than people in the top three-quarters for telomere length.

"Overall, individuals with shorter telomeres had nearly twice the mortality rate of people with longer telomeres," Cawthon said.

Telomere length is measured in base pairs of DNA. The average length at birth is 8,000, but as people age, the average drops to around 3,000 base pairs. Telomere lengths of those in the study ranged from 1,930 to 4310 base pairs.

Although the study correlated telomere length with increased heart disease and infectious disease mortality, the researchers still aren't sure exactly what that means. But the study findings raised three possibilities: * Shorter telomeres increase disease mortality risks and it's possible that a medical intervention to lengthen telomeres could increase longevity.

* Shorter telomeres do not increase the risk of dying, but are markers of an underlying cause of heart disease and infectious disease, perhaps a fundamental process of aging.

* People in the study with shorter telomeres already were ill and telomere length was simply a sign of disease.

"The most exciting possibility suggested by the study is that if we could do some sort of medical intervention and lengthen people's telomeres, they would live longer and healthier lives," Cawthon said.

It may be possible, for example, to introduce the gene that produces the enzyme that makes telomeres longer.

Even if short telomeres do not raise mortality risks directly, but are merely a marker of an underlying cause of age-related disease, measurements of telomere length still may lead researchers to the genes that regulate rates of aging in people, according to Cawthon.

Telomere shortening is accelerated in dyskeratosis congenita, a genetic disorder in which patients suffer premature onset of multiple age-related diseases. The median age of death for people with the disorder is 16.

The Utah researchers had hypothesized that telomere shortening in people without the disorder also would contribute to mortality in multiple age-related diseases.

Evan C. Hadley, M.D., associate director of geriatrics and clinical gerontology at the National Institute on Aging of the National Institutes of Health (NIH), said the study bears follow-up.

"This is a very interesting finding ... But, as the authors note, the association between telomere length and mortality doesn't prove that telomeres cause increased mortality risk--they may just be a marker, reflecting other processes that are the real culprits," Hadley said. "We need further study to clarify this."

The NIA provided funding for the study.

Along with Cawthon, the researchers included Ken R. Smith, Ph.D., professor of family and consumer studies; Elizabeth O'Brien, Ph.D., and Anna Sivatchenko, M.D., of the Huntsman Cancer Institute at the University of Utah; and Richard A. Kerber, Ph.D., also of the Huntsman Cancer Institute and associate professor of oncological sciences at the University of Utah School of Medicine.