But in a paper published in PLOS Genetics, researchers led by Stuart Kim, professor of developmental biology and genetics at Stanford University, questions that dogma. He found that on the contrary, centenarians may have fewer of the genes that contribute to major chronic diseases. That doesn’t mean that people who live to their 100s also don’t possess some protective anti-aging genes as well, but Kim’s study shows that they don’t experience as much disease as people who are shorter-lived.Kim’s team came to that conclusion after conducting a novel type of genetic analysis. Most attempts to look for genes related to aging compare the genomes of centenarians and people with average life spans and pick out the regions where the maps differ. Those are potential targets for aging, but, as Kim notes, they could also be red herrings. “Because you search through hundreds of thousands, and now millions of variants, there is a lot of noise. So it makes it difficult to see the signal amidst all the noise.”
To purify the signal, Kim layered another piece of information on this comparison. He made the assumption that disease genes can reduce the chances of someone reaching their 100s, and focused just on known disease-causing genes in his analysis. “With that, we can make better guesses about what is really bad for becoming a centenarian,” he says.
The filtered analysis pumped out five major regions of interest for longevity. Four are familiar; they involve the gene connected to Alzheimer’s, an area involved with heart disease, the genes responsible for the A-B-O blood type and the immune system’s HLA region that needs to be matched for organ transplants to avoid rejection. These four have known connections to longevity. The Alzheimer’s gene, ApoE, for example, is linked to shorter life span, while the heart disease variants are involved in directing a cell’s life span and the O blood type is known to be connected to better health outcomes and survival.
The fifth region was one that had never been linked to longevity before, and Kim admits that not much is known about how it might contribute to longer life, except that mutations in the gene region can contribute to neurological diseases such as ALS and that in fruit flies, other mutations help the insects to live longer.
“It seems intuitively obvious, that avoiding disease is part of the strategy of becoming a centenarian,” says Kim. “But there is a really, really strong dogma in the field that there was no depletion of disease genes in centenarians, and that all of their survival benefit was coming from protection from anti-aging genes. I think they were wrong.”
Those previous studies that pointed to this anti-aging effect over the effect of fewer disease-causing genes were generally smaller, and might not have isolated the signal from the noise.
Kim’s team shows that the way centenarians reach their second century may involve more than just being blessed with anti-aging genes. “We found that, at least in part, they live longer because they don’t get sick,” he says. He also readily admits that they may also benefit from some anti-aging factor that researchers haven’t uncovered—yet.