Why Do Some People Live Past 100? Genome May Hold Clues to Longevity


Photo by Flickr user the Waltherfamily.

Scientists call them supercontrols: people who have lived past 100, and have somehow evaded the age-related diseases most can’t escape after a century of life, such as heart disease, stroke and Alzheimer’s disease.

They are the subject of the 2013 Archon Genomics X Prize, which will award $10 million in prize money to those researchers who can build the best, fastest, cheapest, most accurate whole human genome. Or at least the best combination of those qualities. Each team will have 30 days and must achieve an accuracy of no more than 1 error per 1,000,000 bases. (1 error in 100,000 bases is not uncommon now.)

The aim is to create a “medical grade” genome. In other words, a genome that doctors can use to develop personalized medical treatment for a patient.

The journal Nature Genetics announced on Wednesday that the subjects for the contest will be centenarians. This means that several teams of researchers will sequence the genomes of 100 people over the age of 100. After the contest, data from the sequences will be made publicly available for science.

And we’re not talking about just any centenarians. The hope is to choose folks who have lived heartily past 100 — the older, the better — who have developed the fewest age-related illnesses, and who ideally come from a family also rich in longevity. People for whom the act of getting sick has been compressed to the very end of their lives.

“One idea is that these people, people who have evaded the diseases of aging have been dealt a healthy hand,” said Myles Axton, editor of Nature Genetics. “Another is that they’re carrying rare variants that most of us don’t have that protect them.”

Thomas Perls, director of the New England Centenarian Study and a professor of medicine at Boston University, calls them genomic pioneers. “These are kind of ideal controls,” said Perls, who has acted as a consultant for the prize. “Whereas if you just grab anybody as a control, you don’t know if they will develop disease in the future. [The centenarian subjects] will become valuable controls for the sequencing done for various diseases down the road.”

There’s mounting evidence that many centenarians may carry protective gene variants that predispose them against age-related diseases. Researchers like Perls will use the data from the sequences to study this.

“Knowing what these genes are and how they interact will be very helpful,” Perls said. “I think it’s going to be a mix of common and rare variants. Some we know already, some we don’t, and I don’t think it’s going to be one or two or three. I think it’s going to be hundreds.”

Of course, they’ll ultimately need to sequence more than 100 genomes to identify protective variants, especially the rare ones. But the hope is that doctors can use that information to develop therapies that protect against disease.

“What is it that makes people age in a healthy way — that makes organs age in a healthy way?” Axton said. “The great thing about the challenge is that the goal is specified, but the way there is not specified … We don’t know what will be brought to bear.”

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