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.

Found in: and Genes & Cells