Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Gonda Building, 695 Charles Young Drive South, Los Angeles, CA, USA.
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Geroscience. 2021 Oct;43(5):2413-2425. doi: 10.1007/s11357-021-00438-7. Epub 2021 Sep 5.
Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.
人类 DNA 甲基化数据此前曾被用于开发高度准确的衰老生物标志物(“表观遗传时钟”)。随后的研究表明,类似的表观遗传时钟也可以为老鼠和许多其他哺乳动物开发。在这里,我们基于使用定制 Infinium 阵列(HorvathMammalMethylChip40)对高度保守的哺乳动物 CpG 进行分析而生成的新型 DNA 甲基化数据,为普通狨猴(Callithrix jacchus)描述了表观遗传时钟。从这些数据中,我们开发并提出了适用于全血样本的两种狨猴表观遗传时钟。我们发现,人类-狨猴相对年龄时钟在另外两种非人类灵长类动物:长尾猕猴和恒河猴中表现出中等高的年龄相关性。在另一组狨猴中,我们测试了雷帕霉素(一种已被证明可延长老鼠寿命的药物)是否会改变通过狨猴表观遗传时钟测量的狨猴的表观遗传年龄。这些时钟未检测到雷帕霉素对狨猴血液表观遗传年龄的显著影响。普通狨猴与其他哺乳动物不同,因为不可能根据 DNA 甲基化数据构建准确的性别估计器:随机森林性别预测器的准确性(66%)明显低于其他哺乳动物(接近 100%)。总的来说,这里为普通狨猴开发的表观遗传时钟有望用于估算野生出生动物的年龄,并用于该物种的抗衰老研究。