Genes Influence Aging into 90s—But Not Beyond .
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ariants of a gene thought to be linked to longevity appear to influence aging into the 90s, but do not appear to affect exceptional longevity, or aging over 100, a study co-authored by School of Public Health and School of Medicine researchers has found.
The research challenges previous findings that indicated some variants of the gene, FOXO3, played a role in exceptional longevity, the research team said in a study in the Journals of Gerontology: Biological Sciences. Paola Sebastiani, professor of biostatistics, was the study’s senior author. It was led by Harold Bae, former graduate student in biostatistics at SPH and now assistant professor at the College of Public Health and Human Sciences at Oregon State University, with co-authors including Thomas Perls, professor at the School of Medicine.
People who live into their 90s or 100s—beyond the typical life expectancy of near 80 for adults—can offer important lessons about healthy aging, the authors said. Centenarians usually experience slower aging throughout their lives, live independently well into their 90s, and spend only the last few years of their exceptionally long lives with significant diseases or disabilities.
Unlike average aging, in the case of people who live into their late 90s and even into their 100s, centenarians appear to benefit from combinations of longevity-enabling genes that likely protect against age-related diseases and disability, said Sebastiani.
She said FOXO3 could be playing such a role for people who live into their early- to mid-90s. The gene has gained attention over the last 10 years as a possible contributor to longevity, but despite a lot of study, the mechanism by which FOXO3 helps people remains unclear.
“It certainly seems to play a role, but we have more work to do to understand how and why,” Sebastiani said.
The researchers examined genetic data from blood samples of 2,072 extremely old subjects from four centenarian studies: The New England Centenarian Study; the Southern Italian Centenarian Study; the Longevity Genes Project at Albert Einstein College of Medicine; and the National Institutes on Aging-Funded Long Life Family Study. Researchers conducting centenarian studies such as these are working together to discover the biological mechanisms that enable remarkable aging.
The researchers who published the paper found that while FOXO3 did seem to play a role in longevity to a degree, that role did not generally affect living to ages 96 or older for men, or 100 for women—the oldest one percent of the population.
“We attended presentations and read scientific papers claiming associations between FOXO3 variants and longevity, yet when we tested for these associations among centenarians, we were unable to reproduce the findings,” said Perls, director of the New England Centenarian Study at Boston Medical Center. “We suspect that part of the reason may be because these earlier claims were coming from studies made up mostly of people in their 80s and 90s, and not those in their 100s.”
The new findings likely will prompt new areas of research, as scientists continue to look for answers about genetic components of longevity and exceptional longevity.
“There’s still more to learn about this gene,” Perls said. “We know for sure it influences aging, but what we show is that it may not be a key player in achieving truly exceptional age.”
The research was supported by grants from the National Institute on Aging; the William M. Wood Foundation; and the Paulette and Marty Samowitz Family Foundation.