ScienceDaily (July 2, 2010) — By analyzing the DNA of the world’s oldest people, Boston University scientists said Thursday (7/1/2010) they have discovered a genetic signature of longevity. They expect soon to offer a test that could let people learn whether they have the constitution to live to a very old age.
The researchers, who studied more than 1,000 people over the age of 100, identified a set of 150 unique genetic markers that, taken together, are linked to extreme longevity. They acknowledged they didn’t know all the genes involved, nor their exact function in extending old age.
The researchers developed a novel Bayesian statistical approach to analyze genotype data from more than 1,000 centenarians and several control groups, and to identify those SNPs that were most predictive of being centenarians or controls. The team began by using the SNPs that were most likely associated with exceptional longevity, and once the researchers identified 150 SNPs, they found that adding more variants did not further improve the ability to predict whether a person was a centenarian or a control subject.
“This is an extremely complex trait that involves many processes,” said lead researcher Paola Sebastiani, a biostatistician at BU’s School of Public Health. Even so, “we can compute your specific predisposition to exceptional longevity.”
While a healthy lifestyle is paramount, such genetic factors appear to become more important the longer we live. Indeed, a variation in a single key gene called FOX03A can triple the chances a person may live past 100, researchers at the Pacific Health Research Institute in Hawaii recently reported.
In research published online Thursday (July 1, 2010) by the journal Science, Dr. Sebastiani, Dr. Perls and their colleagues studied variations in the biochemical code of DNA drawn from members of the New England Centenarian Study, considered the world’s largest comprehensive study of these long-lived people and their families.
The scientists compared the genetic makeup of these centenarians with people who lived more average life spans. The genetic markers they found are scattered across the entire three billion DNA characters of the human genome and touch on at least 70 known genes. Depending on personal habits, diet, injuries, accidents and other factors, these genes boost an individual’s chances of survival in the lottery of life, the scientists reported.
The information allowed the BU researchers to identify those predisposed to exceptional longevity with 77% accuracy in controlled tests, they reported.
“This is a major breakthrough,” said Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, who studies the genetics of longevity but was not involved in the project. “It shows you that 150 markers [among millions] are all you need to distinguish between people who live to 100 and people who don’t.”
Besides looking at which genetic variants were associated with longevity, the authors looked into whether the absence of disease-associated variants also played an important role. They did this by analyzing how many disease-associated variants each centenarian had, compared to each of the controls. Their analysis found little difference between the two groups, suggesting that the presence of genetic variants associated with longevity is of more importance than the absence of disease-associated variants.
If these findings are confirmed, they would suggest that “predicting disease risk using disease-associated variants may be inaccurate and potentially misleading, without more information about other genetic variants that could attenuate such risk” the authors commented.
Overall, the authors said, their preliminary data “suggest that exceptional longevity may be the result of an enrichment of longevity-associated variants that counter the effect of disease-associated variants and contribute to the compression of morbidity and/or disability towards the end of these very long lives.” They added that “further investigation is needed to understand how and why these variants collectively predispose for exceptional longevity.”
“Now, we are going to have to find out what all these genes are, what they do, and if there is a way we can affect them,” said geriatrics expert Bradley Willcox, who was not involved in the Science paper. He is a principal investigator of the Hawaii Lifespan study and the Okinawa Centenarian Study, which involve analysis of thousands of aging men.
