Genetic study Western Hunter-Gatherer genetic ancestry contributes to human longevity in the Italian population

[Tautalus]

Abstract

The genetics of human longevity has been primarily studied using classical methods developed in genome-wide association studies. With the recent advances in paleogenomics, it is now possible to investigate to what extent ancient population ancestries contribute to complex traits. In this study, we explored the role of ancient genetic components in human longevity by focusing on the Italian Peninsula, whose genetic heritage includes several past genetic ancestries that have contributed to the current European genetic make-up. We analyzed genome-wide data of 333 Italian centenarians and 690 geographically matched healthy controls, and compared their genetic composition to 103 ancient genomes representative of the main past European population ancestries. Our findings indicate that Italian centenarians have a higher genetic affinity with Western Hunter-Gatherer (WHG)-related ancestry compared to controls, according to PCA and f4-statistics. Logistic regression models based on supervised admixture revealed a significant association between higher WHG ancestry and the centenarian status. Additionally, residual-based predictive analysis showed that centenarians exhibit a significantly higher WHG contribution independent of the genetic structuring of the general Italian population. By painting the chromosomes of modern Italians, we also showed a significantly higher number of WHG alleles at pro-longevity SNPs. In the present study, we demonstrate the contribution of ancient genetic components to the longevity phenotype. In particular, we showed a greater contribution from Western Hunter-Gatherer-related ancestry to Italian centenarians, thus suggesting that this pre-Neolithic genetic component, which has been linked to population shifts occurring within Europe after the Last Glacial Maximum, could be beneficial for longevity today.
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Western Hunter-Gatherer genetic ancestry contributes to human longevity in the Italian population - GeroScience

The genetics of human longevity has been primarily studied using classical methods developed in genome-wide association studies. With the recent advances in paleogenomics, it is now possible to investigate to what extent ancient population ancestries contribute to complex traits. In this study...

link.springer.com

 

[Vitruvius]

Rather interesting. When I first saw the title I assumed the reason being was due to Sardinians retaining a level of ~15% WHG, which is very high relative to the rest of Italy and southern Europe. Sardinia is of course an already well known blue zone. It appears however that the correlation was found independent of this understanding:

"Additionally, residual-based predictive analysis showed that centenarians exhibit a significantly higher WHG contribution independent of the genetic structuring of the general Italian population."

If this indeed is true, my next question is why WHG ancestry was selected for longevity in Italy, as we don't seem to see the same phenomenon as strongly central or northern europe, which comparably has a significantly higher WHG contribution. This also begs the question of how much of this WHG is also indeed originally from Mesolithic Italy vs being transported there from other regions by later more mobile steppe populations who were spreading westward while mixing with intermediary areas.

Here is a list of ordered life expectancies per European nation:

List of European countries by life expectancy - Wikipedia

en.wikipedia.org

With the exception of Switzerland the top 6 spots are occupied by southwestern European city states and nations. Italy places at 5th. The general trend seems to show southwestern nations followed by nordic and northwestern nations and then a decline to the lowest lifespans as one goes further and further east in Europe.

Perhaps some of this could be explained due to lifestyle factors but we do see at least a fairly strong and broad West to East correlation.

 

[Tautalus]

WHG ancestry here refer to something more specific than raw WHG percentage. I think that which WHG ancestry matters more than how much WHG ancestry.
Italy is one of Europe’s earliest dense agricultural regions, is a long-term hub for trade, urbanization, and disease exposure and some WHG-linked variants may have been positively selected specifically there, in a very specific environmental and selective context, with strong Mediterranean pathogens, diets, and climate pressures.
The same ancestry label can carry very different functional allele frequencies that may express longevity benefits only in Mediterranean dietary contexts. In northern Europe, the same variants may offer no benefit.
WHG ancestry it is not a universal longevity signal, is not “causal” for longevity. It left us regionally selected preserved genetic variants, whose benefits may emerge only in specific ecological and demographic contexts, Italy being one of them. Northern Europe has more WHG, but Italy may have the right WHG, in the right environment, with the right demographic history.​

 

[Vitruvius]

WHG ancestry here refer to something more specific than raw WHG percentage. I think that which WHG ancestry matters more than how much WHG ancestry.
Italy is one of Europe’s earliest dense agricultural regions, is a long-term hub for trade, urbanization, and disease exposure and some WHG-linked variants may have been positively selected specifically there, in a very specific environmental and selective context, with strong Mediterranean pathogens, diets, and climate pressures.
The same ancestry label can carry very different functional allele frequencies that may express longevity benefits only in Mediterranean dietary contexts. In northern Europe, the same variants may offer no benefit.
WHG ancestry it is not a universal longevity signal, is not “causal” for longevity. It left us regionally selected preserved genetic variants, whose benefits may emerge only in specific ecological and demographic contexts, Italy being one of them. Northern Europe has more WHG, but Italy may have the right WHG, in the right environment, with the right demographic history.​

You make a very strong thesis. This is perhaps similar to how light hair and light eyes was selected amongst purely EEF populations in the Baltic. EEF of course did not start out majority blonde haired and blue eyed, but enough natural selection due to low sunlight was able to modify the abnormal phenotype to become what would be normal for this particular area.

It is feasible we could see a similar phenomenon under the guise of certain genes which were ultimately derived from WHGs but were strongly selected for in specifically Italy. If this true my question now is how longevity past reproductive age becomes selected for at all in any population in the first place.