Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2120887119. doi: 10.1073/pnas.2120887119. Epub 2022 May 17.
DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species. Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death. We also present two highly accurate human–dog dual species epigenetic clocks (R = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.
DNA 甲基化图谱被用于开发衰老的生物标志物,称为表观遗传时钟,这些时钟可以非常准确地预测实际年龄,并有望通过推断健康状况来预测生物年龄。表观遗传时钟最初是为监测人类衰老而构建的,但它们的基本原理似乎在进化上是保守的,因为它们现在已经成功地应用于许多哺乳动物物种。在这里,我们描述了可靠且高度准确的表观遗传时钟,这些时钟适用于 93 个家犬品种。甲基化图谱是使用哺乳动物甲基化阵列生成的,该阵列利用了在所有哺乳动物物种中都保守的 DNA 序列。构建犬类表观遗传时钟是为了估计年龄和平均死亡时间。我们还提出了两个高度准确的人类-犬双重物种表观遗传时钟(R = 0.97),这可能有助于将针对长寿和预防医学开发的抗衰老治疗方法从犬类应用(或反之亦然)。最后,全基因组关联研究揭示了可能是品种体重与寿命呈反比关系的个体甲基化位点。总的来说,我们描述了强大的生物标志物,可用于测量犬类的衰老和潜在的健康状况。