Epigenetic aging in cows is accelerated by milk production

DNA methylation has proven to be the most promising age-predictive biomarker in mammals resulting in the emergence of ‘epigenetic clocks’ that describe the relationship between methylation levels and age. Using Targeted bisulfite Sequencing, we evaluated blood DNA-methylation data from 96 domesticated cows (<i>Bos Taurus</i>) of which 88 were adults and 8 were calves. This allowed us to measure DNA methylation across three thousand regions in the genome that were conserved across mammals. The significant association of age with the changes in DNA methylation enabled us to construct an epigenetic clock that predicts the age of cows to within nine months. We also investigated whether factors exist that moderate the association between epigenetic age and actual age and found that milk production levels significantly increase the rate of epigenetic ageing, suggesting that the stress of excessive milk production might be accelerating epigenetic ageing in cows.

DNA甲基化（DNA methylation）已被证实为哺乳动物中最具潜力的年龄预测生物标志物，由此催生了用以描述甲基化水平与年龄间关联的「表观遗传时钟（epigenetic clocks）」。本研究采用靶向亚硫酸氢盐测序（Targeted bisulfite Sequencing）技术，对96头家牛（<i>Bos taurus</i>）的血液DNA甲基化数据展开分析，其中88头为成年个体，8头为犊牛。该研究设计使得我们能够检测哺乳动物基因组中3000个保守区域的DNA甲基化水平。借助年龄与DNA甲基化变化之间的显著关联，我们成功构建了一款可将奶牛年龄预测误差控制在9个月以内的表观遗传时钟。此外，本研究还探究了是否存在调控表观遗传年龄与实际年龄之间关联的因素，结果发现产奶量水平显著加快了表观遗传衰老速率，这表明过量产奶所带来的应激可能加速了奶牛的表观遗传衰老过程。