From alchemists and the Philosopher’s Stone to Ponce de Leon and the Fountain of Youth, history is full of stories of people searching for a way to extend life indefinitely.  In recent years, discoveries about the biology of aging have brought us closer to that dream than ever before.  Now 23andMe is asking you, our customers, to help push science even further by participating in our new Longevity Survey.

Human life expectancy is now close to 78 years. Back in 1900, the average person was expected to live only about 47 years.  The oldest person so far whose age was verified by official documents was Jeanne Calment of France, who died at the spectacular age of 122 in 1997, but one aging researcher at the University of Texas Health Science Center has bet that someone will have lived to be 150 years old by the year 2150! Our improved understanding of health and human biology, including the development of antibiotics, has helped to fuel this huge increase in how long we expect to live.

We all know that environmental factors and lifestyle factors are important when it comes to attaining a ripe old age.  You have to eat right, exercise enough, and avoid all those vices like smoking and too much drinking.  But it’s not all what you do and how you live that determines whether you’ll live a long life, and if you do, whether you’ll be in good shape.  Genes are involved in aging as well.

A lot of the work on understanding the genetic factors involved in aging have been done in laboratory animal models.  Mutations in a gene called daf-2 in soil worms can double their lifespan.  Similar mutations can make fruit flies live up to 80% longer, and mice 30% longer than normal.   Daf-2 makes a protein that’s similar to one that binds insulin, the hormone that regulates glucose intake from your blood.  Some have speculated that daf-2 mediates the the longevity effects of dietary restriction (consuming a significantly reduced number of calories without malnutrition), which has been shown to extend the lifespan of both mice and monkeys.

That’s all well and good if you’re a worm or a fly or a mouse, but what about people?  Well, there’s some progress in understanding aging in us too.  Studies have shown that variants in the APOC3 gene and the FOXO3A gene are associated with longevity.  On the flip side, researchers have discovered that  mutations in the RECQL2 gene cause Werner’s syndrome, a disease that manifests as accelerated aging.

Our DNA is likely to hold many more of the secrets to living a long, healthy life.  That’s why 23andMe wants to do research to understand more about what genes can tell us about aging and longevity.  We’re working with experts in aging research from across the country, and you can join us!  Start by taking our Longevity Survey, which simply asks about the ages of some of your family members.  Hopefully together we can make discoveries that will help people enjoy even more healthy golden years.

ShareThis

Even if you do everything right – exercise, healthy eating, no smoking– whether or not you’ll make it to the century mark depends to some extent on your genes.

One of the important longevity genes seems to be FOXO3A.  It’s been linked to lifespan in several experimental animal models. In humans, studies have shown that certain variations in the FOXO3A gene increase the odds of being extremely long-lived.

(See SNPwatch: Mounting Evidence That FOXO3A Contributes To Human Longevity for more about FOXO3A variation and, for 23andMe Complete Edition customers, a link to your data.)

It’s not exactly clear how FOXO3A affects longevity because it’s known to play a part in several important cellular functions, including cell growth, cell specialization, response to oxidative stress and  the regulation of cell death.  Two studies published last month in the journal Cell Stem Cell added to the list of the FOXO3A’s talents.  Renault et al. and Paik et al. showed that in mice FOXO3A and related FOXO genes are involved in maintaining the brain’s ability to generate new cells, a function critical for both normal brain functions and repair in response to natural degeneration or injury.

New brain cells arise from a pool of specialized self-renewing cells called neural stem cells.  The FOXO genes appear prevent the brain from burning through its supply of these important cells prematurely.

“Because [neural stem cells] have been shown to be important for learning, memory, and mood regulation, our findings could give insight into the decline in cognitive function that occurs during aging,” Renault et al. wrote in their report.

More research will be needed to fully understand the role of the FOXO genes in neural stem cells.  Experiments will also be needed to test whether these findings can be extended to humans.

Despite the work that is left to be done, Paik et al. optimistically suggest the new understanding of the importance of the FOXO genes in neural stem cells may help guide the development of drugs that could help improve central nervous system health in the elderly and people suffering from neurodegenerative disease or brain injury.

ShareThis

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.)

ShareThis