DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation in Peromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscus clocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude in Peromyscus. The human-Peromyscus epigenetic clocks are expected to provide a significant boost to the attractiveness of Peromyscus as a biological model.

基于 DNA 甲基化的衰老生物标志物已针对人类和许多其他哺乳动物开发出来，可用于评估压力因素如何影响衰老。鹿鼠（Peromyscus）是一种长寿的啮齿动物，已成为研究衰老、极端环境适应和一夫一妻制行为的信息丰富的模型。在本研究中，我们对白鼠属的 DNA 甲基化进行了详尽的全基因组分析，涵盖不同的物种、种群、性别、组织和年龄组。我们根据使用定制阵列测量的高度保守的哺乳动物 CpG 生成的新 DNA 甲基化数据，描述了不同种类鹿小鼠基于 DNA 甲基化的年龄估计器。鹿小鼠的多组织表观遗传时钟在 3 个组织（尾部、肝脏和大脑）上进行训练。两个人类-白鼠时钟分别准确地测量了年龄和相对年龄。我们展示了与不同条件（如实际年龄、高海拔和一夫一妻制行为）相关的 CpG 和丰富的通路。总的来说，这项研究为研究白鼠一夫一妻制行为和高海拔适应的表观遗传相关性迈出了第一步。人类-Peromyscus表观遗传时钟预计将显着提高Peromyscus作为生物模型的吸引力。