For most centenarians, longevity is written in the DNA

Study reveals many genetic paths to 100

Juan Ponce de León never found his Fountain of Youth, but researchers may have discovered a genetic equivalent hidden in the DNA of centenarians.

Only one in 6,000 people reaches the century mark and just one in 7 million lives to be a supercentenarian — someone who is 110 or older. But a new study, published online July 1 in Science, suggests that more people may have the right genetic stuff for extreme longevity.

In the new study, researchers looked at genetic markers called single nucleotide polymorphisms, or SNPs, in 1,055 centenarians and 1,267 younger people, all of European descent. The scientists found 150 genetic SNP variants linked to extreme longevity.

Initially, the team identified only 33 SNPs found more often in people aged 90 to 114 years but not in a control group made up of people who will presumably live an average lifespan. But, says Thomas Perls, a geriatrician at Boston University School of Medicine who coauthored the new study, the researchers felt that they were still missing part of the story. So biostatistician Paola Sebastiani of the Boston University School of Public Health devised a different statistical method to identify additional SNPs that would improve the team’s ability to predict longevity. The team tested their predictions on a separate group of centenarians and controls. With the 150 SNPs, the researchers could correctly predict who was a centenarian 77 percent of the time.

“Now on one side, 77 percent is a very high accuracy for a genetic model, which means that the traits that we are looking at have a very strong genetic base,” Sebastiani says. On the other hand, the 150 SNPs can’t explain why the remaining 23 percent of centenarians in the study have reached such ripe old ages. It could mean that those people have other, rare genetic variants or lifestyles responsible for their longevity or some combination of the two, she says.

Extrapolating these results to try to predict how long the average person will live would be a mistake, says Nicholas Schork, a statistical geneticist at the Scripps Translational Science Institute and the Scripps Research Institute, both in La Jolla, Calif.

“They’ve identified markers for something, but what that something is remains a mystery,” Schork says. How the combination of genetic markers work together to extend health and life “is the zillion-dollar question.”

Many of the variants have no known function, although some have previously been linked to Alzheimer’s disease, chromosome stability and insulin, Sebastiani says.

Don’t expect the genetic data to lead to a Methuselah pill, Perls says.

“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,” he says. But the research could conceivably lead to treatments that delay diseases such as Alzheimer’s.

Supercentenarians had nearly all of the longevity markers. But most of the over-100 crowd carried different combinations of SNPs that fell into one or more of 19 different genetic profiles. Those results indicate that there are many different genetic paths to longevity and that many different biological processes are involved, Sebastiani says.

Some of the genetic profiles correlated with extreme delays in the onset of diseases such as dementia, heart disease or cancer. Others seem to allow centenarians to withstand the effects of such diseases. Notably, one group of centenarians had almost none of the longevity-associated SNP variants.

The researchers had expected that centenarians would lack disease-associated variants, but that isn’t the case. On average, centenarians in the study had as many disease-associated variants as people in the control groups did. That suggests that the longevity variants may cancel out disease-associated factors.

About 15 percent of people in the general population may actually have what it takes genetically to reach 100, says Perls. “If they’re not hit by a bus, if they’re not in a war, if they haven’t had some other accident happen, maybe they get to fulfill that,” he says. “Now, a bunch of those people may also need to not smoke and not be obese and a number of important lifestyle factors as well.”

Sebastiani says, “One can conjecture that genetically we’re built to live longer,” and longer life expectancies associated with improved public health measures seem to bear that out.

Other studies have shown that genetics account for only 20 percent to 30 percent of a person’s chances of living beyond age 85. Environmental factors, including lifestyle choices such as diet, smoking and exercise habits, are still the most important determinants of longevity.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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