Biggest genetic study of supercentenarians reveals clues to healthy aging

If you eat well, exercise frequently and avoid those detrimental vices, you can reasonably hope to live a long and healthy life. Of course, many age-related diseases seem almost inevitable, whether they catch up with you in your 80s or your 90s. But some people show a propensity for extreme longevity, living healthily well past the age of 100.

Research has shown those who live beyond the age of 100 tend to present extraordinarily healthy signs of aging. They are less likely to have been hospitalized in earlier life and have seemed to avoid many age-related conditions most people battle in their 80s or 90s, such as heart disease or neurodegeneration.

This new study presents a comprehensive investigation of 81 semi-supercentenarians (aged over 105) and supercentenarians (aged over 110). The researchers also matched this cohort against a group of healthy, geographically matched subjects aged in their late 60s. The goal was to genetically distinguish those generally healthy people in their late 60s from those extremely healthy supercentenarians.

Five particular genetic changes were commonly detected in the supercentenarian cohort, concentrated around two genes called STK17A and COA1.

STK17A is known to be involved in DNA damage response processes. As we age, the body’s DNA repair mechanisms become less effective. Accumulated DNA damage is known to be responsible for some signs of aging, so increased expression of STK17A can favor healthy aging by preserving DNA repair processes in old age.

Reduced expression of COA1 in the supercentenarians was also detected. This gene plays a role in communications between a cell’s nucleus and mitochondria.

“Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species," explains senior author on the new study, Cristina Giuliani. "We showed that this is true also within humans, and data suggest that the natural diversity in people reaching the last decades of life are, in part, linked to genetic variability that gives semi-supercentenarians the peculiar capability of efficiently managing cellular damage during their life course."

The researchers also found the supercentenarians displayed an unexpectedly low level of somatic gene mutations, which are the mutations we all generally accumulate as we grow older. It is unclear why these older subjects have avoided the age-related exponential increase usually seen with these kinds of mutations.

“Our results suggest that DNA repair mechanisms and a low burden of mutations in specific genes are two central mechanisms that have protected people who have reached extreme longevity from age-related diseases,” says Claudio Franceschi, another senior author on the study.

The new research was published in the journal eLife.