Epigenetics of the far northern Yakutian population.

BACKGROUND:Yakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below - 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the local population have not been studied before. RESULTS:This work reports the first epigenetic study of the Yakutian population using whole-blood DNA methylation data, supplemented with the comparison to the residents of Central Russia. Gene set enrichment analysis revealed, among others, geographic region-specific differentially methylated regions associated with adaptation to climatic conditions (water consumption, digestive system regulation), aging processes (actin filament activity, cell fate), and both of them (channel activity, regulation of steroid and corticosteroid hormone secretion). Further, it is demonstrated that the epigenetic age acceleration of the Yakutian representatives is significantly higher than that of Central Russia counterparts. For both geographic regions, we showed that epigenetically males age faster than females, whereas no significant sex differences were found between the regions. CONCLUSIONS:We performed the first study of the epigenetic data of the Yakutia cohort, paying special attention to region-specific features, aging processes, age acceleration, and sex specificity.