While genomic research on the super-old is still in its very early stages, what's most fascinating is what the researchers are not finding.
Ninety is old. One hundred is very old. But 114 -- that is the rarest of ages. Of the 7,000,000,000 people on Earth, four (FOUR!) have reached that plateau. Recently, the genomes of two 114-year-olds were published by a Boston University team in Frontiers in Genetics of Aging. Though one older person is believed to have had her genome sequenced, the new duo are the oldest people to have had their genomes published.
People who live past 110, so-called supercentenarians, are sought after by scientists who want to know what clues their genomes might hold for how to make everyone healthier and longer-lived. These two subjects were drawn from a larger group of 115 supercentenarians within the New England Centenarian Study. It has taken the researchers 15 years to build up this long list of very, very, very long-lived people.
While genomic research on the super-old is in its very early stages, what's fascinating is what the researchers are not finding. These people's genomes are fundamentally the same as other people's. They are clearly very special, but not in ways that are obvious.
"We tried to see whether these two genome sequences differ in something dramatic, like major structural or functional differences, but we didn't see any major differences," explained Boston University statistician Paola Sebastiani, who worked on the new paper. "They also don't differ in the number of disease-associated variants. We have seen this several times now. People who live very long carry as many disease pre-disposing variants as people in the general population."
One of the patients had a gene variation associated with higher rates of colon cancer and was, in fact, diagnosed with advanced colon cancer in his 70s. "The cancer was treated with surgery and this person went on to live another 40 years."
"They must have something that allows them to avoid the bad effects of variants associated with diseases," Sebastiani said.
If we know one thing, it's that such things are not the result of individual gene variations but require many different genes acting in concert.
"It's a phenomenon where many things go right at the same time. These people retain their cognitive functions until the end of their lives. They do not have cardiovascular disease. Parkinson's disease is totally absent," said Sebastiani. "When you see many genes involved, even if we have variants that are common in the population, you have to have them all at the same time. That becomes very, very rare."
Think of it like a lottery where you need to get a hundred or a thousand numbers correct. It's not hard to get a few right, but getting them all is remarkably improbable. (Also, you have to not get hit by a bus or killed in a war while you wait to see if you won.)
The supercentenarians are particularly interesting to people who study genetics because, as Sebastiani explained to me, they help find the genetic signal amid the environmental noise that partially determines how long a person lives.
"If reaching the average life expectancy, in the 80s in this country, the environment plays a major component. Your genes say very little about your ability to live that long," Sebastiani said. "When you look at older and older ages, in the tradeoff between environment and genetics, the genetics play a bigger and bigger role."
With the rapidly falling costs of gene sequencing, the field of centenerian genomics is about to explode. The Archon X-Prize aims to sequence the genomes of 100 centenarians. It's a good thing the old-timers are so willing to donate to researchers.
"These are very frail subjects," Sebastiani said. "To take blood from them is quite tough, but when they can physically sustain this, they are happy to help science."