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

Vincenzo Iannuzzi; Stefania Sarno; Marco Sazzini; Paolo Abondio; Claudia Sala; Maria Giulia Bacalini; Davide Gentilini; Luciano Calzari; Federica Masciotta; Paolo Garagnani; Gastone Castellani; Edgardo Moretti; Maria Cristina Dasso; Federica Sevini; Zelda Alice Franceschi; Claudio Franceschi; Davide Pettener; Donata Luiselli; Cristina Giuliani

doi:10.1093/emph/eoad034

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

Evol Med Public Health. 2023 Oct 16;11(1):397-414. doi: 10.1093/emph/eoad034. eCollection 2023.

Authors

Vincenzo Iannuzzi¹, Stefania Sarno¹, Marco Sazzini^{1

2}, Paolo Abondio³, Claudia Sala⁴, Maria Giulia Bacalini⁵, Davide Gentilini^{6

7}, Luciano Calzari⁷, Federica Masciotta⁸, Paolo Garagnani^{4

9}, Gastone Castellani⁴, Edgardo Moretti¹⁰, Maria Cristina Dasso¹¹, Federica Sevini⁴, Zelda Alice Franceschi¹², Claudio Franceschi¹³, Davide Pettener¹, Donata Luiselli³, Cristina Giuliani¹

Affiliations

¹ Department of Biological, Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Bologna, Italy.
² Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), Interdepartmental Centre, University of Bologna, Bologna, Italy.
³ Department of Cultural Heritage (DBC), University of Bologna, Ravenna Campus, Ravenna, Italy.
⁴ Department of Medical and Surgical Science (DIMEC), University of Bologna, Bologna, Italy.
⁵ IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
⁶ Department of Brain and Behavioral Sciences, Università di Pavia, Pavia, Italy.
⁷ Bioinformatics and Statistical Genomics Unit, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan, Italy.
⁸ Department of Statistical Sciences 'Paolo Fortunati', Alma Mater Studiorum, University of Bologna, Bologna, Italy.
⁹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁰ Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Instituto de Biología y Medicina Experimental de Cuyo, CCT CONICET, Argentina.
¹¹ Centro de Investigaciones en Antropología Filosófica y Cultural (CIAFIC), Buenos Aires, Argentina.
¹² Department of History and Cultures, University of Bologna, Bologna, Italy.
¹³ Laboratory of Systems Medicine of Healthy Aging and Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, Russia.

Abstract

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 Wichí, 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 Wichí (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 Wichí 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.

Keywords: DNA methylation; South America; epigenetic clocks; genomic history; human aging.