Evolutionary and ecological determinants of human longevity

Human longevity and aging are shaped by a complex interplay of biological processes and ecological factors, with a significant variability across human populations. This thesis explores the roles of microevolutionary and ecological determinants in shaping human longevity and biological aging, using case studies from the Gran Chaco region in Argentina (Wichí and Criollos) and modern Italy. Biodemographic analysis revealed no significant impact of prolonged isolation or high kinship on biological aging in the Wichí, as assessed by epigenetic clocks. In contrast, Native American ancestry in the Criollos was associated with accelerated aging, highlighting the influence of genomic history on biological aging. Paleogenomic analysis of the modern Italian population identified contributions from ancient ancestries to longevity, with centenarians showing a stronger affinity for Western Hunter-Gatherer (WHG) ancestry, suggesting that ancient genetic components may contribute to promoting longevity. Paleogenomic analyses were also conducted at candidate gene level on the DLX5/6, a gene locus associated with longevity in mouse models. We identified a high frequency of the rs2240294 variant, linked to reduced DLX5/6 expression in Western Hunter-Gatherers (WHG), supporting an ancient evolutionary origin of certain variants related to extended lifespan. Within the ecological framework, analysis of modern rural and urban Italian individuals revealed higher intrinsic epigenetic age acceleration (IEAA) among those born in rural settings, likely influenced by socio-economic disparities and environmental exposures. Additionally, distinct ecological factors—such as nutrition, living environment, social conditions and infection load—significantly influence biological aging, as measured by epigenetic clocks, in the Wichí and Criollos populations, with the indigenous Wichí experiencing greater epigenetic age acceleration. These findings underscore the complex, multifactorial nature of aging as shaped by biodemographic history and ecological contexts, providing valuable insights into the determinants of longevity across diverse human populations.