SNPwatch: Mounting Evidence That FOXO3A Contributes To Human Longevity

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Want to live long enough to get a birthday wish from Willard Scott?   It may depend on more than just eating right and getting plenty of exercise.   Your DNA could play a part too.

Last year a report showed that variations in the FOXO3A gene are associated with longevity in Japanese men.   Now a separate research group has confirmed these findings in a European population.   These results, published online this week in the Proceedings of the National Academy of Sciences, add credence to the idea that FOXO3A is, as the authors call it, a “ susceptibility gene for prolonged survival” — a condition that many of us hope to develop.

Flachsbart et al. looked at a collection of FOXO3A variations in a sample of German men and women.   They found that several variations slightly increased the odds of being long-lived (aged 95-100).   When the sample was split into nonagenarians (people in their 90s) and centenarians (those 100+), the researchers found that the effects of the FOXO3A SNPs were much stronger in those that had made it to the century mark.   For example, having one or two As at rs2802288 increased the odds of making it to 100 by about 1.5 times.

“Centenarians may be particularly enriched for beneficial variants in ‘longevity assurance genes’,” the authors write.

Rs2802288 is located very close to rs2802292, which was one of the SNPs found in the September 2008 report by Willcox et al on Japanese men living in Hawaii.   In that study, men with an A at rs2802292 had 1.91 times odds of living to 95 or older compared to those with two Cs; two As increased the odds by 2.75 times.   Unlike in the German study, where two copies of the long-lived version had no more effect than one, each copy of rs2802292 appeared to increase the odds of longevity in the Japanese sample.

The authors investigated several FOXO3A SNPs in French and Dutch samples.   There was no statistically significant association between the SNPs and longevity in these groups, although there were some suggestive results in the French sample.

According to the authors, there is good reason to believe that variations in FOXO3A could contribute to healthy aging.   The protein encoded by the gene has been shown to control insulin sensitivity and influence risk for coronary heart disease and type 2 diabetes.   The fact that the association has now been observed in two genetically diverse groups makes the evidence even stronger.   More work will be needed to work out all the details, however.

“The future challenge is to investigate whether the observed discrepancies in the strength and kind of the FOXO3A effect can be verified and, if so, to clarify whether they are caused by study design, population-and/or gender-specific difference, or some other factors.”

(23andMe customers can look up their data for rs2802288 using the Browse Raw Data feature. This SNP is located very close to rs2802292, which is not currently available.   Customers with Japanese ancestry can use rs2802288 as a proxy for rs2802292, keeping in mind that while the A version of rs2802288 also indicates increased chances of longevity, the exact odds will differ from those cited in the September 2008 study by Willcox et al.)