All mammals progress through similar physiological stages throughout life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects underlying genomic events is unclear. Here, we map the common methylation changes experienced by mammalian genomes as they age, focusing on comparison of humans with dogs, an emerging model of aging. Using oligo-capture sequencing, we characterize methylomes of 104 Labrador retrievers spanning a 16-year age range, achieving >150× coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship that translates dog-to-human years and aligns the timing of major physiological milestones between the two species, with extension to mice. Conserved changes center on developmental gene networks, which are sufficient to translate age and the effects of anti-aging interventions across multiple mammals. These results establish methylation not only as a diagnostic age readout but also as a cross-species translator of physiological aging milestones.

所有哺乳动物在整个生命过程中都会经历相似的生理阶段，从早期发育到青春期、衰老和死亡。然而，这种保守的生理学在多大程度上反映了潜在的基因组事件尚不清楚。在这里，我们绘制了哺乳动物基因组随着年龄增长而经历的常见甲基化变化，重点是人类与狗的比较，这是一种新兴的衰老模型。使用寡核苷酸捕获测序，我们表征了跨越 16 岁年龄范围的 104 条拉布拉多犬的甲基化组，在哺乳动物同线块内实现了 >150 倍的覆盖率。与人类甲基化组的比较揭示了一种非线性关系，该关系将狗与人的年数转化为时间，并将两个物种之间主要生理里程碑的时间对齐，并扩展到小鼠。保守变化以发育基因网络为中心，这足以转化年龄和抗衰老干预措施对多种哺乳动物的影响。这些结果确立了甲基化不仅可以作为诊断年龄读数，而且可以作为生理衰老里程碑的跨物种翻译器。