A Long Life Is Genetically Different From A Healthy One

How do some people live for nearly a century free of chronic disease? Scientists have identified genetic clues that could explain why.

They’ve made it far in life, 80 years and counting. Yet they’re conspicuously free of the afflictions that often crop up in old age: diabetes, heart disease, cancer, dementia. They are a rare breed, the “Wellderly.”

That’s the name researchers have given a group of older adults who could unlock the genetic secrets not just to a long life, but a healthy one.

“Longevity is somewhat man-made because you can now do so much for a person — you can put them on life support and live forever,” Eric Topol, who oversees the Wellderly study as director of the Scripps Translational Science Institute in La Jolla, California, told BuzzFeed News. “Short of that, you can certainly treat cancers and heart disease and neurodegenerative diseases, and keep people alive but not healthy.”

What his team wants to understand is why some elderly people have managed to avoid developing any chronic conditions. “For all these years of genomics, we’ve been focusing on diseases,” Topol said. “There just hasn’t been enough work on the health span” — that is, the number of years a person maintains good health.

The first study out of the Wellderly project, published on Thursday in the journal Cell, suggests that healthy aging and longevity, while related, also have distinct genetic differences.

The Scripps researchers found that more than 500 Wellderly group members had significantly lower genetic risks for Alzheimer’s and heart disease, compared to a control group of younger adults. A handful of the Wellderly group also possessed rare genetic variants that the scientists suspect help protect against cognitive decline.

Although the research team stopped short of crediting these genetic differences as the direct causes for healthy aging, they said their findings highlight the need for follow-up study into why these differences exist and what role, exactly, they play in healthy aging. To that end, they have made their data available online.

Independent scientists are intrigued by the findings, but caution that they are preliminary.

“The study is certainly interesting and suggests there may be a key difference between healthy aging and exceptional longevity,” Brian Kennedy, CEO of the Buck Institute for Research on Aging in Novato, California, told BuzzFeed News. “But we certainly need to replicate the study and get more information.”

In late 2007, Scripps researchers began fanning out across retirement communities in search of subjects. (It was initially dubbed the “Healthy Elderly” study, and recruitment was slow, Topol said. “When we renamed it ‘Wellderly,’ everybody wanted to be in it.”) To date, they’ve assembled a group of more than 1,300 people between 80 and 105. They mostly live in the U.S., skew male, and exercise often. Compared with people in their age bracket in the general U.S. population, the Wellderly are also leaner, slightly more likely to smoke (probably because smoking was more common when they grew up), and highly educated.

The Scripps researchers aren’t the only ones analyzing the DNA of people who have lived well beyond the normal lifespan. Researchers at the Albert Einstein College of Medicine in New York City have been studying healthy adults over 95, and scientists in British Columbia are beginning a study of “super seniors” 85 and up.

But what makes the Wellderly group special, Topol said, is that none of its members have a history of chronic conditions.

In the new study, 511 Wellderly members’ genomes were compared to a group meant to represent the general population: 686 adults sequenced by another research institute for a different study about genetic markers of premature births.

First, Topol’s team looked at genetic variants previously linked with longevity. But those variants didn’t crop up more in the Wellderly than controls. That suggested that the genes driving healthy aging are somewhat different from those driving longevity.

Then the scientists looked at the two groups’ risks for the top five leading causes of death with known genetic associations. They saw no difference in the groups’ genetic risk for cancer, stroke, or type 2 diabetes, and Topol said his team didn’t know why. But they did find that Wellderly members were less likely to carry the genetic variant most commonly linked to Alzheimer’s, as well as other variants associated with the disease.

What’s more, relatively few Wellderly carried genetic markers associated with heart disease compared with the control group, although this contrast was weaker than the Alzheimer’s one.

The researchers also reported a surprising finding about a gene known as COL25A1, which has been linked to the brain plaques associated with Alzheimer’s. Ten Wellderly members carried ultra-rare variants on this gene. Although that small sample size makes it hard to draw conclusions, the presence of these variants may indicate they play a role in staving off cognitive decline, Topol said.

The study adds to previous work reporting that the genetic variant most commonly linked to Alzheimer's shows up less often in elderly people, noted Angela Brooks-Wilson, a professor of biomedical physiology and kinesiology at Simon Fraser University in British Columbia.

“There may be protective genetic factors that help people achieve healthy aging,” Brooks-Wilson told BuzzFeed News. So looking for drugs that could mimic that protection “would be very worthwhile,” she said.

The Wellderly could also serve as a control group in other scientists’ aging research. “This is a crisply defined group of truly healthy advanced-age people,” Topol said. “We hope that’s going to prove to be an anchor reference for many others in the future.”


Angela Brooks-Wilson noted that the study builds on previous research finding the genetic variant most commonly linked with Alzheimer's to be less common in elderly people. An earlier version of this story misstated her remarks.

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