At 107, George Eberhardt puts his longevity down to diplomacy. “I say, never say no to your wife,” quips the New Jersey centenarian. But Dr Thomas Perls thinks that there is something more to Eberhardt’s feat.
As a geriatrician, Perls has been studying centenarians since the 1990s. “These individuals age much more slowly than a lot of people,” he explains. “And they markedly delay or escape age-related diseases, so there’s a real human model for incredibly healthy ageing.”
Perls claims that his studies have accumulated significant evidence of a “genetic competence” that gets stronger in line with age. “As a result,” he says, “we want to find the genetic variations that enable such healthy ageing.”
Although Perls and his peers around the world have been looking at centenarian DNA for decades, a much more focused project is now getting underway: the Archon Genomic X Prize (AGXP). This bold endeavour seeks to find a fast and cheap way to sequence a person’s entire genetic code. Competitors will have to test their methods on the DNA of centenarians. And Perls has convinced Eberhardt to be one of the participants. In total, Perls needs the DNA of 100 people over age 105 to supply their DNA to this unique science competition, the prize for which is $10m.
The contest kicks off in January 2013, by which time Perls must have recruited all 100 DNA donors. “The search is only just beginning,” he says, joking: “I have a special whistle - I just blow and they come running!”
Prize fighters
As the founder and director of Boston University’s New England Centenarian Study, Perls notes that centenarians have become twice as common as when he first began to study them in 1995. That is why he now prefers to find folks who, like Eberhardt, are older than 105. “We get even happier with super-centenarians, who are 110-plus,” he says, adding that only one in every five million people live that long.
Studying the DNA of those who reach such an astonishing age is the bedrock of the AGXP. The project is the latest bold initiative of Dr Craig Venter, the most famous figure in commercial genomics. Previously named one of Time magazine’s 100 most influential people, Venter and his team grew tired of the slow pace of the public initiative to sequence the entire human genome. With private funding, Venter accelerated the project, delivering the first sequence in 2000, three years ahead of schedule. Venter is persistently controversial for his futuristic predictions on synthetic biology and the applications of gene sequencing. And now he is pushing for a new clinical standard for whole gene sequencing. In classic Venter style, the method will be established through a contest, the AGXP.
“The goal of this competition is to push the industry to develop more accurate, faster and more cost-effective sequencing technologies,” Venter explained at the contest’s launch. “While many new technologies have been developed over the last decade and many human genomes have been sequenced, there is still no technology that can produce a highly accurate, reproducible human genome usable for diagnostics and medical treatment.”
With that goal, Venter has teamed up with the X Prize Foundation, a non-profit organisation that runs major public competitions to encourage technological innovation for the benefit of mankind. Inspired by the Orteig prize of 1919 for the first non-stop flight between New York and Paris (won by Charles Lindbergh), the X Prize Foundation has already found a successor to the space shuttle. It has also partnered with the Bill and Melinda Gates Foundationto find a better diagnostic tool for tuberculosis.
And now the organisation is joining US healthcare giant Medco to promise $10m in winnings for the first team to sequence 100 whole human genomes within the 30-day deadline and for less than $1,000 each. Competing scientists will be required to sequence the same 100 genomes: from the 100 centenarians found by Perls.
Variety is the dice of life
The holy grail of decoding such antique DNA is the identification of protective variants, versions of genes that somehow stop their host ageing as quickly as people who carry a different version, or prevent them from dying from common diseases. Eberhardt and his cohort are thought to benefit from a combination of several hundred protective gene variants that increase longevity. Exploring how these tricks work could lead to a greater understanding of biochemical pathways, which could ultimately inform how scientists develop new medication. “Knowing what pathways are important will help us understand diets and other exposures we don’t know about that slow ageing,” Perls explains.
One institute intrigued by the results that could be offered up by the AGXP is the UK-based PHG Foundation, a research body focused on translating genomics advances into healthcare. “Not getting common diseases will be a combination of genetic and environmental factors,” says PHG’s Dr Philippa Brice. “It’s not something that you inherit like a disease – otherwise you’d have families of old people. But what it is? That’s an interesting one.”
One answer could be found by examining how the participants’ DNA has frayed over time. DNA is packed into chromosomes, which are capped by special bits of DNA called telomeres in much the same way that the end of a shoelace is protected by aglets. Each time a cell divides, the chromosomes it carries are replicated. During this process, the telomeres at the ends are snipped a little. As you age, the telomeres become shorter, meaning that in successive divisions, the DNA close to the telomeres is more prone to being snipped itself.
“There’s been a lot of work looking at telomeres and ageing,” observes Brice. “So they’ll be looking for something there.” At the moment, geneticists are by and large busy investigating the causes of specific diseases rather than wider health issues such as those caused by telomere deterioration. And yet disease-focused research has so far not crafted the silver bullets many scientists thought it would. As Perls notes, “Finding genes associated with diseases has been going on for a long time, but not much in terms of helping people has come out of that.”
Without applying genetic data to healthcare, Brice argues, medicine will not be able to develop as it should. Unless researchers work out how to incorporate their knowledge of DNA into healthcare, our understanding “will be limited”. Brice adds that as a longer-term complement to the AGXP, the innovative use of genetic data in medicine “is going to be really important”.
Scientists therefore place great value on the genetic information served up by centenarians. For his part, Eberhardt is both excited and puzzled by the idea that his DNA could carry some fascinating secrets. “It’s brand new to me,” he says.
Main image courtesy of pedrosimoes7.
Do you know a centenarian? They might be eligible to become one of our “genomics pioneers.” For more information, please visit:
http://genomics.xprize.org/life-at-100-plus
And meet some of our centenarians and read some of their life stories.