TORONTO — Researchers have identified a group of genetic signatures shared by people with exceptional longevity — those rare folks whose lifespans reach the century mark and beyond.
In a study published online Thursday by the journal Science, Boston University researchers report that a spate of 150 genetic variants predicted with 77 per cent accuracy those people who were 100-plus or close to reaching that ripe old age.
The scientists compared the presence of the genetic variants in the genomes of more than 1,000 Caucasians born between 1890 and 1910, with a median age of 103, and almost 1,300 control subjects. The oldest in the first group died at 119.
They found that about 45 per cent of the oldest subjects — those 110 and older, dubbed supercentenarians — had genetic signatures with the highest proportion of longevity-associated markers.
“Centenarians are indeed a model of aging well,” said principal investigator Dr. Thomas Perls, director of the New England Centenarian Study.
“A lot of people might ask who would want to live to 100, because they think they have every age-related disease under the sun and are on death’s doorstep and certainly have Alzheimer’s. But this isn’t true.”
Previous studies of long-lived people have shown that about 90 per cent are disability-free at the average age of 93, he explained.
“So they very much compress their diseases or their disability to the very end of their lives. And supercentenarians compress both disability and disease even further.”
Reaching an extremely advanced age is a rare phenomenon: those who hit the century mark account for about one in every 6,000 people in industrialized counties. Supercentenarians who reach or pass 110 are even rarer — about one in seven million.
Far more women than men make up the ranks of the very old, but Perls said men tend to have less age-related disability and disease than their female counterparts.
“Centenarian men tend to be functionally quite fit compared to the women,” he said in a teleconference from Boston. “But women seem much better able to handle diseases.”
Surprisingly, the researchers found that the centenarian and control group did not differ substantially when it came to genetic diseases that predispose people to such age-related illnesses as heart disease and dementia.
“These results suggest that what makes these people live very long lives is not a lack of genetic predisposition to disease, but rather an enrichment of longevity-associated variants that may be protective,” added so-author Paola Sebastiani, a professor of biostatistics at Boston University. “It may even cancel the negative effect of disease-associated variants.”
“We think these analyses represent an important step forward in our understanding of exceptional longevity as well as anti-aging,” she said.
However, the researchers cautioned that good genes aren’t the only key to long life — environmental and lifestyles factors also likely play significant roles in whether a person will have a birthday cake topped with 100 candles or more.
And they caution that much more study is needed by their team and other research groups to see if their findings hold up and just what they mean.
“Clearly we realize that this is a very complex genetic puzzle,” said Perls, noting that the 150 markers involve 70 genes spread across the chromosomes.
“I feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians, but rather to make a dent in the onset of age-related diseases like Alzheimer’s.”
Still, the researchers say a “chip” could be made with the 150 genetic variants that could test whether someone is likely to enjoy an exceptionally long life, while other testing could look for those genes known to be linked to dementia and other diseases of advancing years.
“Could these signatures tell a physician and their patients who’s going to be at increased risk for a particular disease sooner and can this lead perhaps to interventions that might help them?” asked Perls.
“I think that that’s a possibility down the road. That brings up that whole field of personal genomics or medicine and being able to use genetic information in the future to help guide therapy.”
Dr. Brent Richards, whose McGill University lab studies the genetics of age-related disorders, said the paper provides an interesting twist on the use of genome-association studies.
But he suggested the size of the study group is too small to say with certainty that these 150 genetic markers are indeed predictive of someone attaining extreme longevity or dying at an earlier age.
The genetic profiles of much larger groups of centenarians will need to be analysed, said Richards, who was not involved in the research.
“Their accuracy is quite good, but that needs to be done in external cohorts (study groups),” he said from Montreal. “The accuracy that they have reported is not sufficient to be able to take any one individual off the street and tell them how long they’re going to live.”
Perls agreed that a test based on the findings is “not ready for prime time,” although there will likely be companies who use the information to create such a commercial product aimed at individuals.
The Boston researchers are not seeking a patent on the genetic markers, and will make the information openly accessible to other scientists and the public on the New England Centenarian Study website at www.bumc.bu.edu/centenarian.