Pair bonding slows epigenetic aging and alters methylation in brains of prairie voles

The quality of romantic relationships can be predictive of health consequences related to aging. DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how pair bonding impacts aging. Prairie voles (Microtus ochrogaster) have emerged as a model to study social attachment among adult pairs. Here we describe DNA methylation-based estimators of age for prairie voles based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for voles was trained on 3 tissue sources (ear, liver, and samples of brain tissue from within the pair bonding circuit). A novel dual species human-vole clock accurately measured relative age defined as the ratio of chronological age to maximum age. According to the human-vole clock of relative age, sexually inexperienced voles exhibit accelerated epigenetic aging in brain tissue (p = 0.02) when compared to pair bonded animals of the same chronological age. Epigenome wide association studies identified CpGs in four genes that were strongly associated with pair bonding across the three tissue types (brain, ear, and liver): Hnrnph1, Fancl, Fam13b, and Fzd1. Further, four CpGs (near the Bmp4 exon, Eif4g2 3 prime UTR, Robo1 exon, and Nfat5 intron) exhibited a convergent methylation change between pair bonding and aging. This study describes highly accurate DNA methylation-based estimators of age in prairie voles and provides evidence that pair bonding status modulates the methylome.