The secret of an incredibly long, incredibly healthy life eludes us still.
That’s the main finding of a major multi-year effort, led at Stanford University, to sequence the full genomes of 17 of the 22 oldest people in the United States, all “supercentenarians” over the age of 110. While it’s still exciting to live past 100, it is incredibly rare to live past 110. There are only a few dozen people in the world alive at any time who are verified to reach this age. You often read about their birthdays in news reports; usually these people are remarkably free of the age-related diseases that plague most elderly.
“At the beginning, we were really hopeful it would be simple,” says Stanford aging researcher Stuart Kim. “It would be like cystic fibrosis, but for longevity–where there is a single gene responsible.”
Kim and his research team knew finding an obvious genetic key to extreme longevity was actually a long shot. Still, they had a number of false hopes as they sifted through mountains of DNA over several years. These leads, however, usually only lasted a couple of sleepless weeks. When comparing the supercentenarians’ genes with those of a less long-lived control group, the scientists couldn’t prove that the most promising gene variant, called TSHZ3, actually did appear more often in those living past 110.
While in the end, the authors, from Stanford, the Institute for Systems Biology, UCLA, and the Gerontology Research Group, concluded that “it is extremely unlikely” that there is a single rare gene shared uniquely by the world’s oldest people, that doesn’t mean they are near giving up their search.
Extreme longevity has throughout history been the subject of endless fascination from scientists, scammers, news reporters, and the public alike; it was always unlikely the fountain of youth would be obvious, even as new genetic sequencing technologies now making more investigations possible.
Steve Coles, the paper’s co-author and director of the Gerontology Research Group, has made it his life’s work tracking supercentenarians around the world with the hope of reversing aging. He helped the research team find and recruit these rare individuals, most of whom are women.
Today, researchers believe that genetics is a main factor in determining unusual longevity. While supercentenarians come from backgrounds of all stripes, and while some live healthy lifestyles and others do not, what supercentenarians all have in common is their unusual health and vigor. They aren’t plagued by heart disease, cancer, or the many other diseases that greatly increase in risk with old age. One woman in the study practiced as a pediatrician until 103. Another drove a car until 107. One subject was found by researchers to have a gene linked to a serious heart condition, which never materialized over a 110-year plus lifespan.
Often their families also live until very old ages, too. Kim remembers visiting Soledad Mexia, a woman who lived to be 114 in San Diego. There, at a birthday party, were six generations of her family gathered together.
“When we saw the family, you just sit down and you say, okay, this is really interesting. The supercentenarian, she looks 90. The child is 90, but looks 65. The grandchild was 60, but she looked 40. They are aging slower than normal people,” he remembers.
The paper’s authors are making all the genomic data public, so others can help mine it for patterns common to supercentenarians and expand the dataset. Kim believes it’s very possible that the answer involves many different gene variants that code for related proteins, rather than a single one. Another potential key could be in the vast, barely understood parts of the genome that don’t directly code for proteins but may control how other genes are expressed. That work is for the longer term.
Ultimately, a growing field of aging researchers–joined by several new Silicon Valley biotech companies–hope to build on such research to one day slow down the aging clock, and stave off the quality-of-life degrading diseases that come with old age.
“Much better than trying to fix the 85-year-old, is trying to keep the 85-year-old in a healthy state to start,” Kim says. “We can slow down the clock of aging in animals, and that’s what we should be trying to do for people, too.”
There is still a long road ahead, however.