Genetic Secrets of Longevity Revealed

In the largest study of long-lived individuals to date, researchers at Vanderbilt University have identified a pair of genes linked to the risk of developing Alzheimer’s disease. The gene variant associated with the highest genetic risk of late-onset Alzheimer’s disease (AD) is known as APOE-ε4.

Another variant of the same gene, APOE-ε2, is believed to provide protection against Alzheimer’s disease.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and led by scientists from the Vanderbilt University Medical Center, examined the prevalence of APOE-ε4 and APOE-ε2 among so-called “superagers” — people aged 80 and older whose cognitive abilities are comparable to those of individuals 20–30 years younger.

These older adults were 68% less likely to carry the APOE-ε4 gene compared with people aged 80+ who had Alzheimer’s dementia. Most notably, the likelihood of having APOE-ε4 among superagers was 19% lower than among cognitively normal participants in the same 80+ age group, reports Scientific Russia.

“This was the most striking finding: although all adults who reach the age of 80 without a diagnosis of clinical dementia demonstrate exceptional aging, our study shows that the phenomenon of ‘superaging’ can be used to identify a distinct group of older adults with reduced genetic risk for Alzheimer’s disease,” said Leslie Gaynor, associate professor of geriatric medicine, who led the study together with Alaina Duran.

The researchers also found for the first time that the protective APOE-ε2 variant was more common among superagers. Their likelihood of carrying APOE-ε2 was 28% higher than among cognitively normal individuals aged 80+, and 103% higher than among participants aged 80 and older with Alzheimer’s dementia.

The category of “superagers” partially included individuals aged 80+ whose memory performance exceeded the average level of cognitively normal participants aged 50 to 64. The study included participants from diverse racial and ethnic backgrounds. Globally, the prevalence of APOE-ε4 is 13.7%, while in this study it reached 43.9%.

“As interest in longevity grows,” Gaynor said, “our findings support the idea that the superager phenotype may be useful in the search for mechanisms that confer resilience to Alzheimer’s disease. To date, this is the largest study to identify differences in the frequency of APOE-ε4 alleles based on superaging status, as well as the first to demonstrate an association between APOE-ε2 allele frequency and superaging. We expect these results to spark further interest in how these variants may influence the development of clinical Alzheimer’s dementia and the phenomenon of superaging as a whole.”

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