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Finding Your Longevity Genes

Centenarians share genetic quirks, and you might too.

En español | You may think of longevity as just more time to struggle with the diseases and disabilities that can come with getting older, but studies show that people who do live very long lives remain free from diseases and disabilities until quite late in life. Now Boston University researchers have discovered some of the genetic quirks that appear to delay the arrival of age-related conditions in people who live to 100 and beyond.

The team performed genetic tests on a large group of centenarians to look for those quirks, called genetic variants or single-nucleotide polymorphisms (SNPs), that are more common in centenarians than others. They then used a novel statistical approach to analyze the data and produce a “genetic signature”—made up of 150 SNPs and involving about 70 genes—that is predictive of living to 100, the team reported July 1 in the journal Science.

People’s lifestyle and environment play a very big role in how long they live. But pinpointing the SNPs common to centenarians is one step toward the very complex process of understanding how genes pave the way to truly golden years, the researchers say. It may also lead to a test that will tell people if they have what it takes genetically to live past 100.

Discovering the genes

The team conducted the New England Centenarian Study at Boston Medical Center by comparing the genetic profiles of about 800 individuals, ages 95 to 119, with a group of noncentenarians. Of the centenarians, 85 percent were women and all were Caucasian. The group is studying other ethnicities but doesn’t yet have results available.

The team found that 90 percent of the centenarian group could be subdivided into 19 subgroups or clusters.

Specific clusters shared unique characteristics, such as when or whether they got different age-related diseases. Although men and women had similar genetic signatures, the men were generally healthier than the women, says coauthor Thomas Perls, M.D., director of the New England Centenarian Study.

They beat the risks

Despite being what Perls calls “models of healthy aging,” centenarians had a similar number—compared with the noncentenarians—of the genetic variants known to increase a person’s risk of disease, the team found.

“This suggests that what makes these people live very long lives is not a lack of genetic predisposition to disease but rather an enrichment of [genetic variants] that may be protective and may even cancel the negative effect of disease associated variants,” says coauthor and biostatician Paola Sebastiani of Boston University School of Public Health.

Whether these genetic charms can be bottled and sold is another question. “I look at the complexity of this [genetic longevity] puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians,” Perls says. However, he is optimistic that understanding centenarians’ genetic traits that postpone the onset of age-related diseases, such as dementia, will lead to strategies for delaying the conditions in others.

Longevity tests for all?

The genetic signature that the Boston team found could conceivably be used to predict whether anyone has the genetic make-up to live past 100, says Perls. They are making their computer program available to other researchers and do not plan on patenting it. But he doesn’t think it should be made available to the public anytime soon.

A government-funded scientist, Perls suspects that companies will probably try to market a longevity test for consumers. But he warns that it’s important to understand what consumers, insurance companies and others may end up doing with this information.

“What would you do if you are told you absolutely don’t have the signature for longevity—would you go do a lot of risk taking behaviors … or does it give you impetus to take all the more better care of yourself?” he asks.

Less than perfect

Another deterrent to making their computer program available to the public is that currently its accuracy rate is only 77 percent. That’s a good score for a genetic model and shows that longevity does “have a very strong genetic basis,” says Sebastiani. But the 23 percent error rate also means that other genes, the environment and lady luck are having their say as well.

While only about 0.02 percent, or 1 in 6,000 people, live to age 100 in industrialized countries, about 15 percent of the study’s control group has the genetic signature of a centenarian, the team reports. This may suggest that more people than we thought “have the potential, at least genetically, to survive to an exceptional age,” they report.

Do the genes cause longevity?

The Boston team used statistical tools to tease out genetic variants common to long-lived people, but now the task is to see which of these variants may cause exceptional longevity, says geneticist S. Michal Jazwinski, director of the Tulane Center for Aging at the Tulane University Health Sciences Center in New Orleans.

His team’s approach is to study a few genes at a time that are known to have anti-aging functions. Using a “candidate gene approach,” he and his colleagues found three genes that interact to reduce age-related changes at the cellular level, they report in a paper published online June 21 in Aging Cell. Among study participants, the frequency of this three-gene combination continuously increased with age, including after age 100, Jazwinski reports.

Paving your own way to a long life

As we continue our wait for the fountain, or pill, of long life, what’s a person to do? Studies of long-lived groups, such as the Seventh Day Adventists, show that exercising, abstaining from smoking and heavy alcohol use, eating a healthy diet, staying engaged with others, and enjoying productive pursuits are all associated with a long and prosperous life.

Or you can listen to one of those lucky 1 in 7 million individuals. “I never had children—that’s the reason I reached 111!” says Bernice Madigan, laughing. She will celebrate her 111th birthday with a crowd on July 24 at her niece’s farm, where she now lives. She takes a daily walk, keeps her weight down and has always loved playing piano and reading. She also had a job for the federal government and a husband whom she loved. But really, she says, “I have no idea how I reached this age. I just feel normal, that’s all.”

Tina Adler is a freelance writer who covers health, science and the environment.

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