Longevity's secret code revealed

Extreme longevity is associated with a select group of genetic markers, according to a new study of centenarians, people living at least 100 years. Using these markers, researchers can predict a person's ability to become a centenarian with 77 percent accuracy.

Researchers say they can predict your
likelihood of becoming a centenarian
with 77 percent accuracy
Image: Flickr,
user linkurl:Dark_Ghetto28;http://www.flickr.com/photos/dark_ghetto28/407953159/

"Exceptional longevity is not this vacuous entity that no one can figure out," said lead author linkurl:Thomas Perls,;http://www.bu.edu/alzresearch/team/faculty/perls.html the director of the linkurl:New England Centenarian Study;http://www.bumc.bu.edu/centenarian/ at Boston Medical Center. "I think we've made quite some inroads here in terms of demonstrating a pretty important genetic component to this wonderful trait." "This paper is an important breakthrough in the field," agreed linkurl:Jan Vijg,;http://www.einstein.yu.edu/home/faculty/profile.asp?id=11318 a gerontological geneticist at the Albert Einstein College of Medicine, who did not participate in the study. Perls recruited Boston University biostatistician linkurl:Paola Sebastiani;http://people.bu.edu/sebas/research.htm to design the genetic analysis, published on Science Express today (July 1). The study chose 1000 non-related Caucasian centenarians and super-centenarians (those living 110 years or longer) from the New England Centenarian Study, which has been following people since 1995. The centenarians were compared to younger Caucasians with similar genetic backgrounds. The researchers compared the frequency of 300,000 single-nucleotide polymorphisms (SNPs) in both groups, then looked for the SNPs that appeared most unique to the centenarians. They sequentially added additional markers down the line, increasing the specificity and sensitivity of the prediction algorithm until the results plateaued. Ultimately, the algorithm contained 150 SNPs that predicted a person's chances of reaching 100 with 77 percent accuracy. The team is developing a software program for use by other researchers, companies, and individuals to analyze a genetic sequence and determine the likelihood of extreme longevity. Less than half of the SNPs were located in areas associated with functioning genes. Some linked to the insulin pathway, some to genes associated with Alzheimer's disease (including the ApoE4 gene variant, which is a genetic risk factor for the disease) and dementia. Many of the SNPs point to more basic biological processes, such as chromosomal instability, muscle function and control of the immune system. "Biologically what they show is that many many different processes are involved in achieving these exceptionally old ages," said Sebastiani. Of course, the researchers could only compare centenarians to younger controls, some of whom may eventually become centenarians themselves. However, given that it is such a rare trait -- only one in six thousand people reaches 100 or older -- the researchers said this potential confounder likely had minimal impact on the findings. The centenarians were placed into smaller groups based on their SNP profiles. Some of the groups showed special characteristics, like those who survive the longest or those with the most delayed onset of age-related diseases. There was one cluster of centenarians that did not carry many of the SNPs associated with longevity. These could be people who lived really healthy lives, or harbor rare variants linked to longevity, the authors suggested. Even though the centenarians survived so long, the researchers found that they have similar levels of a large set of disease-associated genetic risk factors as the controls, including risk factors for Alzheimer's, diabetes, and cardiovascular disease. This seems to indicate that long-life indicators also somehow mask disease traits. "You could conceivably produce a chip that would help predict people's genetic predisposition for exceptional longevity," said Perls, cautioning that such a test would carry serious ramifications. The study's approach to unraveling the intertwined combination of genetic markers underlying disease could be used to learn more about other complicated genetic diseases like diabetes, Parkinson's, Alzheimer's and cardiovascular diseases, said Sebastiani. The paper "tells us we should really look closely at aging and longevity if we want to learn more about diseases," said Vijg. P. Sebastiani, et al. "Genetic signatures of exceptional longevity in humans," Science Express, July 2010
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[26th April 2004]