Questions have focused on the analytic platform used to find about 150 genetic variations linked to longevity

By Tina Hesman Saey

Web edition: July 10, 2010
Print edition: July 31, 2010; Vol.178 #3 (p. 10)

Just like the fountain of youth, a study that purported to find genetic secrets to longevity may be a myth, critics say.

Researchers led by Thomas Perls and Paola Sebastiani from Boston University reported July 1 in an online publication in Science that they had identified 150 genetic markers that distinguish centenarians from people with average life spans with 77 percent accuracy.

Almost immediately the study came under fire because of a technical flaw. Most of the controversy stems from the devices used to take the genetic fingerprints of a small number of people in the study. Known as DNA or SNP chips, these devices probe thousands of genetic markers called single nucleotide polymorphisms, or SNPs. These markers are places in the genome where most people have one letter of the four-letter DNA alphabet — such as an A — and a smaller percentage of people have a different letter — a G, C or T.

All of the chips used in the study were manufactured by Illumina, a San Diego-based biotech company. But one of the several lines of chip the study used, called the Illumina 610 array, has flaws that could prevent researchers from correctly identifying some SNPs. That may introduce bias into the study and throw off the results.

Ironically, the team’s statistical analysis of the data — commonly a trouble spot for SNP studies — was very careful, says Nicholas Schork, a statistical geneticist at the Scripps Translational Science Institute and the Scripps Research Institute, both in La Jolla, Calif.

“There are many things in the paper that they did to protect themselves against error, but this is one that slipped through the cracks and may not even have been on their radar,” he says.

While other researchers gave the BU researchers plenty of feedback on their analysis of the data when the team presented the results at scientific meetings, “they probably were never challenged by someone saying, ‘artifacts on the Illumina 610. Beware.’”

“The jury is still out on the degree to which this problem might affect their results,” Schork says. “If it turns out that the whole thing was an artifact, that would be surprising.”

Some critics also question whether the study found too many genetic markers associated with exceptional longevity.

“We went into this research expecting there would be few longevity genes,” says Nir Barzilai, who conducts research similar to the BU group’s as director of the Institute for Aging Research at Albert Einstein College of Medicine in New York City.

But the definition of “few” ranges from one researcher’s estimate of four to another’s of 2,000, he says. His own preliminary data, generated using a different population of people and different SNP chips, also indicate that about 150 SNPs separate the exceptionally long-lived from people who live an average life span.

Barzilai and the BU team also agree on another important point. People who live to 100 and beyond have just as many genetic variants associated with disease as anyone else. But what centenarians have, and the vast majority of the rest of us lack, are longevity genes.

The BU researchers validated their original results when they performed the statistical analysis on a separate group of centenarians and younger people, and came up with the same answer. That indicates that either the model is correct or that both the original set of data and the data used to replicate the experiment are tainted with questionable SNPs. “It might be a garbage in, garbage out thing,” Schork says.

“I don’t know that people should be burned at the stake for this. It’s a mistake, but an honest mistake,” Schork says. “I don’t know that the artifact completely undermines the study.” The only way to know for sure is to redo the analysis minus the faulty data — a step the researchers told Science they are already taking.