No shortage of dangerous DNA

The genome of a 115-year-old woman is mined for secrets to healthy aging

MONTREAL — A Dutch woman who lived to 115 years old credited her longevity to pickled herring, refraining from smoking and limiting alcohol. But scientists are looking to the woman’s genetic blueprints, hoping to uncover the secrets of successful aging.

Any genetic secrets are still buried in the DNA that makes up the woman’s genome, but it has become clear that she did not lack genetic variants that may predispose other people to heart disease, Alzheimer’s and other aging-related illnesses, geneticist Henne Holstege of the VU University Medical Center in Amsterdam said October 14 at the International Congress of Human Genetics. Instead, the woman may have carried variants that protected her from the ravages of age.

What those protective variants might be remain a mystery. “We cannot say anything about the genome pieces that have to do with longevity,” Holstege said. The researchers will have to compare the woman’s genetic makeup with that of other extremely long-lived people, as well as average Joes and Janes, to find potential keys to long life.

The woman, Hendrikje van Andel-Schipper, agreed to donate her body to science at age 112. At that time, Holstege’s father, neuroscientist Gert Holstege of the University of Groningen, performed mental tests and found van Andel-Schipper to be at least as mentally sharp as a person nearly half her age.

After van Andel-Schipper’s death from a stomach tumor in 2005, researchers examined her brain and blood vessels for signs of disease that often accompany aging.  They found nothing: She had no sign of the plaques or other degenerative proteins that build up in the brains of people with Alzheimer’s disease, and her arteries were clog-free.

Her case seemed to negate the idea that everyone develops dementia if they live long enough. “Here was proof of principle that it doesn’t have to happen,” Holstege said.

Now researchers have compiled genetic blueprints from blood and brain cells of van Andel-Schipper (whom they refer to only as “W115”). Analysis has begun to try to find genetic determinants of long life and to track the mutations that accumulate in a person’s body over a lifetime.  

Van Andel-Schipper comes from a long line of people who exceeded the average life span for their time, including her mother, who lived to be 101. To find out whether she had simply inherited fewer genes that predispose people to disease, the researchers determined how many common disease-associated genetic variants were present in her genome and compared the profile with genetic data from other Dutch people. The data show that van Andel-Schipper did not have fewer disease-associated genetic variants. The result dovetails with previous studies of centenarians indicating that extremely long-lived people probably have protective genetic variants that help them to avoid or survive disease.

Another study, presented by researchers at Duke University, examined the genomes of 13 centenarians for rare genetic variants that might be harmful to a person’s health. People on average carry a couple hundred rare genetic variants that might inactivate proteins or be deleterious in other ways, said Elizabeth Cirulli, the researcher who described the work at the genetics congress. But preliminary data from her study indicate that centenarians may carry 50 or so fewer potentially harmful variants. The result needs to be verified in a larger sample of very old volunteers, Cirulli said.

Holstege and her colleagues hope to finish the complete genetic blueprint from van Andel-Schipper by the end of the year and make the data available to other researchers.

Even when the genome is finished, scientists may have a hard time figuring out what part of van Andel-Schipper’s DNA contributed to her long life, said Goncalo Abecasis of the University of Michigan in Ann Arbor. “You may have 10,000 variants that could tell me 10,000 unique things about you,” he said. Only by comparing genomes from many extremely long-lived people will scientists be able to home in on longevity genes, he said.

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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