November 23, 2009

Genes that Protect Chromosome Tips May Boost Longevity

photo of chromosomes with dots at ends Telomeres, in yellow, at ends of chromosomes. Robert Moyzis, University of California, Irvine, CA; U.S. Department of Energy Human Genome Program.

By studying the genes of dozens of people who've lived to 100, scientists have found gene variants that appear to protect chromosome caps, or telomeres, from deteriorating with age. Longer telomeres were associated with both longer lives and healthier aging.

Telomeres are segments of specialized DNA and proteins that cap the ends of chromosomes and prevent them from unraveling. With each cell division, telomeres erode slightly, although they can be rebuilt by the enzyme telomerase. When telomeres become too short, the cell stops dividing or dies. Telomeres are thought to play key roles in aging, cancer and other biological processes.

Although several studies have tied shortened telomeres to age-related diseases and early death in humans, the underlying genetic mechanisms have not been understood. Dr. Yousin Suh of Albert Einstein College of Medicine and her colleagues searched for links between exceptional longevity, telomere length and 2 genes related to telomerase activity. Their research was funded in part by NIH's National Institute on Aging (NIA), National Center for Research Resources (NCRR) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The scientists focused on Ashkenazi Jews, a mostly homogeneous population long studied for genetic research. A group of 86 "centenarians" ranged in age from 95 to 105 years (average age 97). The researchers also studied 175 of their offspring (average age about 70) and an offspring-matched control group of 93 people whose parents had lived normal lifespans.

As reported in the online edition of the Proceedings of the National Academy of Sciences on November 13, 2009, the researchers found that centenarians and their offspring had significantly longer telomeres than the control group. In addition, longer telomeres were linked to healthier lipid profiles, better cognitive function and a reduced risk of high blood pressure, metabolic syndrome and type 2 diabetes.

The scientists sequenced 2 genes needed to make telomerase: human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC). Particular hTERT variants that don't alter the structure of the actual protein were more common in centenarians than controls. In addition, only centenarians had 2 rare variants of the hTERC gene.

The researchers were also able to associate one particular stretch of DNA sequence within hTERT with both exceptional longevity and longer telomere length.

The researchers believe that the variants they found in centenarians might affect the regulation of these telomerase genes, enhancing their expression and thus improving telomere maintenance.

"Our findings suggest that telomere length and variants of telomerase genes combine to help people live very long lives, perhaps by protecting them from the diseases of old age," says Suh. "We're now trying to understand the mechanism by which these genetic variants of telomerase maintain telomere length in centenarians."

—by Vicki Contie

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