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DNA methylation age analysis of rapamycin in common marmosets
GeroScience ( IF 5.3 ) Pub Date : 2021-09-05 , DOI: 10.1007/s11357-021-00438-7
Steve Horvath 1, 2 , Joseph A Zoller 2 , Amin Haghani 1 , Ake T Lu 1 , Ken Raj 3 , Anna J Jasinska 4 , Julie A Mattison 5 , Adam B Salmon 6
Affiliation  

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.



中文翻译:


普通狨猴雷帕霉素DNA甲基化年龄分析



人类 DNA 甲基化数据此前已被用来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,也可以为小鼠和许多其他哺乳动物开发类似的表观遗传时钟。在这里,我们基于高度保守的哺乳动物 CpG 生成的新 DNA 甲基化数据描述了常见狨猴 ( Callithrix jacchus ) 的表观遗传时钟,这些数据使用定制的 Infinium 阵列 (HorvathMammalMmethylChip40) 进行了分析。由此,我们开发并展示了两种适用于全血样本的狨猴表观遗传时钟。我们发现,人类与狨猴的相对年龄时钟在另外两种非人类灵长类动物:长尾猴和恒河猴中表现出中等程度的高年龄相关性。在另一组狨猴中,我们测试了雷帕霉素(一种可延长小鼠寿命的药物)的干预是否会改变狨猴表观遗传年龄(通过狨猴表观遗传时钟测量)。这些时钟没有检测到雷帕霉素对狨猴血液表观遗传年龄的显着影响。普通狨猴与其他哺乳动物的不同之处在于,不可能根据 DNA 甲基化数据建立准确的性别估计器:随机森林性别预测器的准确度 (66%) 大大低于对其他哺乳动物观察到的准确度(其中接近100%)。总体而言,这里为普通狨猴开发的表观遗传时钟预计将有助于野生动物的年龄估计和该物种的抗衰老研究。

更新日期:2021-09-06
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