Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
Geroscience. 2022 Feb;44(1):447-461. doi: 10.1007/s11357-021-00472-5. Epub 2021 Oct 26.
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经在人类和许多其他哺乳动物中得到开发，可用于评估压力因素对衰老的影响。鹿鼠（Peromyscus）是一种长寿的啮齿动物，已成为研究衰老、适应极端环境和一夫一妻制行为的信息模型。在本研究中，我们对不同物种、种群、性别、组织和年龄组的鹿鼠进行了全面的全基因组 DNA 甲基化分析。我们根据在高度保守的哺乳动物 CpG 上生成的新的 DNA 甲基化数据，基于定制的阵列描述了基于 DNA 甲基化的鹿鼠不同物种的年龄估算值。用于鹿鼠的多组织表观遗传钟是在 3 种组织（尾巴、肝脏和大脑）上进行训练的。两个人类-鹿鼠时钟分别准确地测量年龄和相对年龄。我们介绍了与不同条件（如年龄、高海拔和一夫一妻制行为）相关的 CpG 和富集途径。总体而言，这项研究为研究一夫一妻制行为和适应高海拔的鹿鼠表观遗传相关性迈出了第一步。人类-鹿鼠表观遗传钟有望极大地提高鹿鼠作为生物模型的吸引力。
