Genetic Markers Can Predict Likelihood of Living to Extreme Old Age, Researchers Report in Science

Scientists have discovered a series of genetic signatures that are particularly common in people who live to 100 and beyond, compared to the average population. The findings appear online today, in the 1 July Science Express.

These findings raise the possibility that it might someday be possible for people to learn in advance whether they have the potential to live to a very old age—though lifestyle choices and environmental factors would be important factors too. The results also lay some important groundwork for studying the way multiple genes influence how well we age.

“Centenarians are indeed a model of aging well,” said Thomas Perls, associate professor of medicine at the Boston University School of Medicine and a geriatrician at Boston Medical Center, in a teleconference for journalists. Perls is a coauthor of the study.

“A lot of people might ask, ‘well 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,” said Perls. “We have noted in previous work that 90% of centenarians are disability-free at the average age of 93. So, they very much compress their diseases or their disability towards the very end of their lives, and super centenarians, indeed, they compress both disability and disease even further.”

The research team, led by Perls and Paola Sebastiani, professor of biostatistics at the Boston University School of Public Health, scanned the genomes of over 1,000 centenarians and a similar number of controls. They identified a number of genetic markers that are most different between centenarians and randomly selected individuals.

Because multiple genes must be involved in living to extreme old age, the authors next developed a model that computes the probability that a person will reach exceptional longevity, based on 150 genetic markers. Using this model, the researchers were able to predict with 77% accuracy whether someone could live to be a centenarian.

“Now, on one side 77% is a very high accuracy for a genetic model, which means that the traits that we are looking at have a very strong genetic base,” said Sebastiani.

On the other hand, she said, the 23% error rate is important too, since it could be the result of additional genetic factors that they haven’t yet identified, or lifestyle and environmental factors that also influence a person’s lifespan.

The researchers also broke down the genetic predictions into 19 characteristic groups (or signatures) that correlate with different lifespans beyond the age of 100, and with different patterns of age-related diseases such as dementia, hypertension, and cardiovascular disease. Future studies of these genetic signatures could shed light on specific, different patterns of healthy aging, and they may ultimately be useful for personalized medicine and tailored prevention and treatment strategies.

In the teleconference, the researchers emphasized the need to encourage discussion about how the general public might use information coming from this line of research.

“My hope has always been with the study that we would learn much more about how to get lots of people to live to older age in good health and markedly delay their disability and age of onset of diseases towards the very end of their lives, however long that would be,” said Perls.

“I look at the complexity of this puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians,” he added, “but rather to make a dent in the onset of age-related diseases like Alzheimer’s, for example.”

Links

Listen to Robert Frederick’s Science Podcast interview with the Science authors.

Listen to audio of Thomas Perls and Paola Sebastiani discussing the findings during a press teleconference.