Genes passed down from ancient hunter-gatherers who lived in Europe more than 10,000 years ago may be related to exceptional longevity in Italian centenarians today.
A new genetic analysis of more than 1,000 individuals found that the strongest and most consistent genetic signal among centenarians – people who reach 100 years of age – was an increased proportion of ancestry inherited from a group known as Western Hunter-Gatherers (WHG).
An increase in WHG ancestry of just one standard deviation was associated with a 38 percent higher chance of living to see a 100th birthday, the study found.
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Led by geneticists at the University of Bologna in Italy, the researchers say the study "provides a historical-genomic perspective that reframes the concept of healthy aging and longevity – not as a static or universal state, but as a dynamic phenotype shaped by the interplay of genomic population history and continually changing environmental contexts."
Human longevity is a complex phenomenon influenced by environmental, lifestyle, and genetic factors. But recent studies have found that, although longevity does have a genetic component, the specific variants involved can differ between populations – likely as a result of distinct demographic histories and evolutionary pressures.
Advances in ancient DNA sequencing and population-genetic analysis have opened up a way to ask a new question: Could very old ancestral components, dating back to before farming arrived in Europe, still influence who reaches extreme old age today?
The researchers conducted their analysis on 1,126 genomes – 333 from Italian centenarians; 690 from middle-aged Italians, serving as controls; and 103 ancient genomes, representing the four primary ancestral sources of European genetic diversity, including the WHG group that appeared around 14,000 years ago.
They ran multiple analyses of these genomes, looking for particular signatures that were stronger in the centenarian group than in the control group, and cross-referenced the results with ancient DNA to see whether one of those four groups was the source.
Across all analyses, the only ancestry consistently enriched among centenarians compared with the control group was WHG DNA. Meanwhile, DNA from another group, the Yamnaya pastoralists of the Bronze Age, showed a slight negative association with longevity in women.
"Our analyses … showed for the first time that long-lived individuals exhibit a higher affinity to WHG-related ancestry," the researchers write in their paper. "We propose that the variants involved in this trait may have been introduced into the Italian gene pool at a very ancient time."
The exact mechanism driving this effect is unclear, but the researchers note that WHG ancestry first became prominent in Europe after the Last Glacial Maximum, during a period of rapid climatic change.
They propose that some very ancient genetic variants carried by this group may still favor longevity today, although the specific pathways underlying this effect remain unknown.
By contrast, later ancestries that entered Europe after the Neolithic transition may have carried genetic variants that were advantageous in past environments but less beneficial now.
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The researchers point to evidence that post-Neolithic populations evolved more pro-inflammatory immune alleles in response to higher pathogen loads, denser settlements, and new lifestyles – adaptations that may have promoted survival then, but could contribute to inflammaging and age-related disease today.
Whatever the mechanism, this is the first paper to link exceptional longevity to ancient ancestral components in Europe, showing that the genes we inherit from our pre-Neolithic forebears can still alter the course of our lives today.
"In this light," the researchers write, "biodemographic history and genetic ancestry are not merely confounding factors in genome-wide association studies or in precision medicine studies, but important contributors to contemporary phenotypic variability."
The research has been published in GeroScience.