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Epigenetic clock and methylation studies in the rhesus macaque
GeroScience ( IF 5.3 ) Pub Date : 2021-09-06 , DOI: 10.1007/s11357-021-00429-8
Steve Horvath 1, 2 , Joseph A Zoller 2 , Amin Haghani 1 , Anna J Jasinska 3 , Ken Raj 4 , Charles E Breeze 5 , Jason Ernst 6 , Kelli L Vaughan 7 , Julie A Mattison 7
Affiliation  

Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles underpinning them appear to be conserved at least across the mammalian class. This is exemplified by the successful development of epigenetic clocks for mice and several other mammalian species. Here, we describe epigenetic clocks for the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate in biological research. Using a custom methylation array (HorvathMammalMethylChip40), we profiled n = 281 tissue samples (blood, skin, adipose, kidney, liver, lung, muscle, and cerebral cortex). From these data, we generated five epigenetic clocks for macaques. These clocks differ with regard to applicability to different tissue types (pan-tissue, blood, skin), species (macaque only or both humans and macaques), and measure of age (chronological age versus relative age). Additionally, the age-based human-macaque clock exhibits a high age correlation (R = 0.89) with the vervet monkey (Chlorocebus sabaeus), another Old World species. Four CpGs within the KLF14 promoter were consistently altered with age in four tissues (adipose, blood, cerebral cortex, skin). Future studies will be needed to evaluate whether these epigenetic clocks predict age-related conditions in the rhesus macaque.



中文翻译:


恒河猴的表观遗传时钟和甲基化研究



基因组中特定 CpG 位置的甲基化水平已被用来开发人类、小鼠和其他物种的实际年龄的准确估计器。尽管表观遗传时钟通常是物种特异性的,但支撑它们的原理似乎至少在哺乳动物中是保守的。小鼠和其他几种哺乳动物物种的表观遗传时钟的成功开发就是例证。在这里,我们描述了恒河猴( Macaca mulatta )的表观遗传时钟,恒河猴是生物学研究中使用最广泛的非人类灵长类动物。使用定制的甲基化芯片 (HorvathMammalMmethylChip40),我们分析了n = 281 个组织样本(血液、皮肤、脂肪、肾脏、肝脏、肺、肌肉和大脑皮层)。根据这些数据,我们生成了猕猴的五个表观遗传时钟。这些时钟在对不同组织类型(泛组织、血液、皮肤)、物种(仅猕猴或人类和猕猴)以及年龄测量(实际年龄与相对年龄)的适用性方面有所不同。此外,基于年龄的人类猕猴时钟与另一种旧世界物种长尾猴( Chlorocebus sabaeus )表现出高度的年龄相关性( R = 0.89)。 KLF14启动子内的 4 个 CpG 在四种组织(脂肪、血液、大脑皮层、皮肤)中随着年龄的增长而持续改变。未来的研究需要评估这些表观遗传时钟是否可以预测恒河猴的年龄相关状况。

更新日期:2021-09-07
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