Epigenetic aging differences between Wichí and Criollos from Argentina: Insights from genomic history and ecology

Background and objectives: Epigenetic estimators based on DNA methylation levels have emerged as promising biomarkers of human aging. These estimators exhibit natural variations across human groups, but data about indigenous populations remain underrepresented in research. This study aims to investigate differences in epigenetic estimators between two distinct human populations, both residing in the Gran Chaco region of Argentina, the Native-American Wichi, and admixed Criollos who are descendants of intermarriages between Native Americans and the first European colonizers, using a population genetic approach. Methodology: We analyzed 24 Wichi (mean age: 39.2 +/- 12.9 yo) and 24 Criollos (mean age: 41.1 +/- 14.0 yo) for DNA methylation levels using the Infinium MethylationEPIC (Illumina) to calculate 16 epigenetic estimators. Additionally, we examined genome-wide genetic variation using the HumanOmniExpress BeadChip (Illumina) to gain insights into the genetic history of these populations. Results: Our results indicate that Native-American Wichi are epigenetically older compared to Criollos according to five epigenetic estimators. Analyses within the Criollos population reveal that global ancestry does not influence the differences observed, while local (chromosomal) ancestry shows positive associations between specific SNPs located in genomic regions over-represented by Native-American ancestry and measures of epigenetic age acceleration (AgeAccelHannum). Furthermore, we demonstrate that differences in population ecologies also contribute to observed epigenetic differences. Conclusions and implications: Overall, our study suggests that while the genomic history may partially account for the observed epigenetic differences, non-genetic factors, such as lifestyle and ecological factors, play a substantial role in the variability of epigenetic estimators, thereby contributing to variations in human epigenetic aging. Lay Summary: In the Gran Chaco region of Argentina, Native-American Wichi cohabit with Criollos, an admixed population deriving from intermarriages between Native Americans and the first European colonizers. We analyzed epigenetic estimators to assess biological aging at the individual level and we demonstrated that Wichi exhibit a greater epigenetic age compared to Criollos. A potential role of different genetic histories and a major role in lifestyle and ecological habitats is suggested.