Scientists in La Jolla have completed a long-awaited genetic study of people who manage to live into their 80s and above without significant health issues. Their findings — published in Cell on Thursday — suggest people who live long, healthy lives may have fewer genetic advantages than expected. However, some aging experts warn against reading too much into the results.
Scientists at the Scripps Translational Science Institute launched the “Wellderly” study in 2007. Their goal was to identify a large number of people who’ve reached an advanced age without major medical help, and then study their genes for clues about the secrets of healthy aging.
After sequencing hundreds of “Wellderly” genomes and comparing them with a group of genomes representative of the standard U.S. population, researchers found some genetic protections against cognitive decline and heart disease. But beyond that, the DNA of the “Wellderly” weren't significantly different from typical genomes.
“Healthy aging is complex,” said Scripps scientist Ali Torkamani, a senior author on the new study. “It’s not totally genetically determined. Actually, it seems like the underlying genetics is pretty weak."
In other words, healthy aging may not be a matter of winning the genetic lottery — the “Wellderly” turned out not to have as many protections lurking in their DNA as one might think.
"Which, in some ways, I think is good news," said Torkamani. "It indicates that we all might have the potential to be ‘Wellderly.’”
The findings diverge somewhat from other human longevity studies, which often focus on centenarians, people who live to 100 and older. These studies tend to find stronger genetic explanations behind long life.
Previous studies have found that centenarians are more likely to have certain variations within the gene FOXO3A, which is thought to help confer longevity. But when Torkamani and his colleagues combed through the “Wellderly” genomes, they did not find a significant boost in FOXO3A compared to standard genomes.
They did find a lower genetic risk for Alzheimer's and coronary artery disease in the “Wellderly," but they did not find decreased risk for other age-related killers like type 2 diabetes and cancer. Additionally, they found no decrease in the number of rare genetic mutations known to boost disease risk.
They did find that “Wellderly” people and centenarians shared similarities in the Alzheimer's-related gene APOE4. They also found that a significant number of “Wellderly” people had a rare variant in another Alzheimer's-related gene, COL25A1. They say researchers working to better understand Alzheimer’s, and potentially develop treatments for it, should look into this gene further.
The Scripps researchers say their analysis shows people who maintain good health into their 80s are genetically different from people who live exceptionally long lives.
Torkamani said these results show that no single gene can guarantee healthy aging. “It’s maybe wishful thinking to think there’s going to be one gene that protects you from all the different diseases you might succumb to before the age of 80,” he said.
The “Wellderly" may age better than most people due, in part, to non-genetic factors. They differ from the general U.S. population in a few key ways. They tend to weigh less, exercise more and have attained higher levels of education.
Counterintuitively, the rate of smoking was slightly higher among “Wellderly” men than in the general population.
One of the study participants, 90-year-old John Rawlings of San Diego, says he never smoked. He grew up playing basketball and doing hard work on an Indiana farm, and says he remains active today.
“I play softball three days a week,” Rawlings said. "The other three days I go to the gym. Sunday I go to church.”
Rawlings said he's only been hospitalized once in his life, after being injured in a farm accident in his early 20s. His two older brothers are still alive at 99 and 94.
Rawlings chalks his “Wellderly” status up to a healthy lifestyle, but he suspects genetics must also be playing a role.
“I think clean living is important,” he said. “But I don’t know that it’s more important than genetics."
Rawlings was among the 511 “Welderly” individuals analyzed for the new study. Torkamani and his co-authors admit this sample size is fairly small, and their results will need verification in future research. Aging researchers who weren’t involved in the study highlighted these limitations when reviewing the results.
Judith Campisi, a professor at the Buck Institute for Research on Aging, told KPBS in an email that she was surprised to see the paper published in a top-tier journal, given the preliminary nature of the results. But she was glad to see the researchers shift focus toward people who reach an advanced age with their health intact.
"The distinction between healthy aging and longevity is, in my opinion, welcome — something the field of aging research has not yet grasped, despite studies (in simpler organisms) suggesting this distinction is important," Campisi said.
However, Thomas Perls — a Boston University professor of medicine who directs the New England Centenarian Study — thinks scientists should continue studying exceptionally long-lived people if they want to find genetic explanations for healthy aging.
"I am not at all surprised by their very soft genetic findings," said Perls. "The authors concede that there is an increasingly strong genetic component to living beyond 100, and that the genetic influence on healthy aging to one's 80s is much less."
Perls said his research and follow-up studies on centenarians have shown "that a combination of many protective variants has a very strong influence on living to very old age in good shape."
Torkamani argued focusing on healthy people in their 80s makes sense, because the healthcare system is getting increasingly better at extending lifespan.
"And you can kind of string someone along to 100 years old," he said. "But that doesn’t necessarily mean they’ve lived a healthy life up to 100 years.”
The Scripps scientists have made their data on the “Wellderly” available to other researchers seeking to find links between genetics and healthy aging.
