Using the largest sample of super-agers to date, scientists have found convincing evidence that supports what many of us have suspected: Longevity isn’t just about healthy lifestyle choices, but also a good draw in the genetic lottery.
Researchers from Vanderbilt University Medical Center investigated what super-agers – people who enter their 80s with the cognitive function of those many decades younger – might have in common. And they found clear genetic evidence that their fundamental biology is playing a big part in living healthier for longer. This supports 2020 research that found the brains of super-agers actually look different, too.
The team used data from the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium, which included 18,080 participants from eight national aging cohorts. The scientists found that compared to people over 80 years with Alzheimer’s disease (AD), super-agers were 68% less likely to carry the Apolipoprotein E epsilon 4 gene – or APOE-ε4 – the well-known AD-risk gene. What's more, when compared to even healthy people in the same age bracket, super-agers were 19% less likely to have the APOE-ε4 gene.
But it's not just about risk reduction, the researchers found. As well as having a much lower rate of carrying this problematic gene, super-agers had a much higher incidence of also having protective DNA, APOE-ε2. Compared to healthy people over 80 years, super-agers were 28% more likely to carry APOE-ε2 – and this jumped to 103% when measured against people with AD in the same age bracket. Essentially, they were twice as likely to have this protective gene.
"This was our most striking finding – although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional aging, our study suggests that the super-ager phenotype can be used to identify a particularly exceptional group of oldest-old adults with a reduced genetic risk for Alzheimer’s disease," said Leslie Gaynor, assistant professor of Medicine in the Division of Geriatric Medicine, who co-led the study.
While "super-agers" is a catch-all term, it's widely used to group together people who are 80 years or older with the cognitive function of healthy adults aged 50 to 64. For some time, scientists have been trying to work out just why these people defy the statistics when it comes to aging – and in turn tend to live healthily for longer.
"With interest in super agers growing, our findings notably encourage the view that the super-ager phenotype will prove useful in the continued search for mechanisms conferring resilience to AD," Gaynor said.
"This is by far the largest study to date to identify differences in APOE-ε4 allele frequency based on super-ager status, and the first study to find a relationship between APOE-ε2 allele frequency and super-ager status," she added. "We would expect these findings to lend continued interest to questions of how these variants may influence development of clinical dementia due to Alzheimer’s disease, as well as to the super-ager phenotype more generally."
While observational, the study sheds light on the role genes may play in why a small subset of people remain cognitively sharp well into their 80s and beyond.
The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
