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Gene game: why some people live longer

July 08, 2010 03:14 am | Updated 03:14 am IST

COMPLEX: Longevity is a complex genetic trait involves many different biological processes. Photo: T. Singaravelou

With improvements in health care, people are living longer than ever before. In developed countries, people can expect to live to be over 80 years of age. Even so, few get to celebrate their 100{+t}{+h} birthday and fewer still become super-centenarians who cross 110. Centenarians form only one in 6,000 of the population in industrialised nations and super-centenarians just one in seven million.

Such longevity has been found to run in families, suggesting a strong genetic component to it. In a paper that was published online recently by Science Express , a team of scientists reported on their quest for genetic factors that help some people live exceptionally long.

The scientists looked for common genetic patterns in a group of some 800 Caucasian centenarians in the United States. These patterns were then compared to those in a large genetically-matched control population.

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To do so, the study examined close to 300,000 single nucleotide polymorphisms across the entire genome of these individuals. (Single nucleotide polymorphisms are instances where a single 'letter' of the genetic code has changed.)

They found 150 such genetic markers. These genetic markers were used to produce a model to compute the predisposition of individuals to exceptional longevity. When the model was tested with another group of centenarians, it achieved an accuracy of 77 per cent.

“Centenarians are a model of healthy aging, as the onset of disability in these individuals is generally delayed until they are well into their mid-nineties,” observed Paola Sebastiani of the Boston University School of Public Health and her colleagues in their paper.

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But it was not that the centenarians had fewer disease-causing genes.

To the surprise of the scientists, these long-lived elderly people as well as individuals in the genetically-matched control group were found to have similar disease-associated genetic factors.

This suggested that it was not lack of a genetic predisposition to disease that allowed centenarians to live a very long life, remarked Dr. Sebastini at a press briefing. Rather, they appeared to have “an enrichment of longevity-associated variance” that may have a protective function.

The 150 markers of longevity were spread over the 23 human chromosomes.

“They confirm our conjecture that this is an extremely complex genetic trait that involves many different biological processes, ”she pointed out.

Some of the markers pointed to genes that were already known to have a role in increasing lifespan. But other markers indicated the involvement of other genes as well.

It was necessary to understand the pathways governed by these genes, which produced such longevity, observed Thomas Perls, one of the co-authors of the paper. Moreover, how these genes interacted, not just with themselves, but also with environmental factors had also to be figured out.

“My hope has always been …. that we would learn much more about how to get lots of people to live to older age in good health,” he said.

“I look at the complexity of this puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians, but rather to make a dent in the onset of age-related diseases like Alzheimer's for example.”

The paper “Genetic Signatures of Exceptional Longevity in Humans” can be found online at http//wwwsciencemagorg/cgi/content/abstract/science.1190532

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