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Scientists track down human longevity genes

By Will Dunham

 
WASHINGTON, Aug 27 (Reuters) - An exhaustive analysis of the DNA of exceptionally long-lived siblings has enabled scientists to find the location of genes that appear to give certain people the ability to live to age 100 and beyond.

The study, appearing on Monday in the Proceedings of the National Academy of Sciences, may not mark the discovery of the mythical fountain of youth sought in vain by Spanish explorer Ponce de Leon 500 years ago.

But the researchers said it certainly will help explain why some people can live decades longer than the average life expectancy, and could pave the way for the development of drugs that mimic what centenarians possess genetically to escape the ravages of aging.

The researchers, led by Louis Kunkel of Children's Hospital in Boston and the Howard Hughes Medical Institute in Chevy Chase, Maryland, and Thomas Perls of Beth Israel Deaconess Medical Center in Boston, found a region in human Chromosome 4 that appears to harbor a gene or genes that confer remarkable longevity.

A search for the genetic characteristics that might account for the disease-resistance and survival advantage enjoyed by centenarians led the researchers to their discovery. While recording the medical histories of centenarians, they learned that many of the subjects had long-lived siblings.

"If you found one centenarian, you would frequently find a second centenarian or a second individual who was in their 90s and in great health. That smacks of genetics right there, to see it being familial," Kunkel said in an interview.

The researchers performed a genome-wide comparative analysis of 137 sets of two or three siblings who were at least 90, in which at least one member of each set was age 98 or older. DNA was extracted from blood of 308 people age 91 to 109. The subjects predominantly were of European descent.

The scientists used 400 markers spread along the entire human genome to find anything the subjects had in common. The research led them to a region on Chromosome 4 that contains between 100 and 500 genes. The researchers believe that the region contains one, or at most a few, longevity-related genes.

THE SEARCH CONTINUES

Kunkel said the researchers hope to find the precise gene or genes responsible for longevity within six months to a year. He said a subtle genetic variation -- called a single nucleotide polymorphism -- appears to be at work, rather than a genetic mutation like those that cause hereditary diseases.

Asked what exactly a longevity gene might be doing to add decades to a person's life span, Kunkel admitted, "We don't have a clue at the moment." But he said there is a 95 percent certainty that the researchers are looking in the right place.

Scientists hope to figure out the biochemical pathways that the responsible gene or genes impact in order to foster longevity. This could lead to the development of drugs that imitate the action of longevity genes, the researchers said.

"We're not trying to find the fountain of youth. If anything, we're trying to find the fountain of aging well," Perls said.

But Kunkel said people should not delude themselves into thinking scientists will be able to invent a pill that will let them live to be 105. "That's not going to happen," he said.

One in 10,000 Americans is a centenarian, exceeding the average life expectancy by 20 years. Scientists have wondered what allowed centenarians to maintain good health for so long.

The researchers speculate that centenarians may age more slowly than everyone else and either greatly delay or completely avoid age-related diseases such as cardiovascular disease, stroke, diabetes, cancer and Alzheimer's disease.

Kunkel said only a small number of genes influence longevity in lower organisms -- just a few genes need to be altered to give a longer life span to round worms and fruit flies -- and that now appears to be true in humans. The prevalent belief among experts in the field of aging had been that as many as 1,000 genes influenced aging.

"There are lots of genes that will influence life span," Kunkel said, referring to those that may predispose some people to various diseases. He said it appears centenarians are spared these bad genes while also benefiting from the presence of a subtle genetic variation that favors great longevity.

11:14 08-27-01
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