Epigenetic clock and methylation studies in the rhesus macaque.

Epigenetic clock and methylation studies in the rhesus macaque.
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DOI:
10.1007/s11357-021-00429-8
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发表时间:
2021-10
期刊:
影响因子:
5.6
通讯作者:
Mattison JA
Mattison JA
中科院分区:
医学1区
文献类型:
--
作者:
Horvath S;Zoller JA;Haghani A;Jasinska AJ;Raj K;Breeze CE;Ernst J;Vaughan KL;Mattison JA

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基因组中特定CpG位置的甲基化水平已被用于在人类、小鼠和其他物种中开发准确的时间年龄估计器。虽然表观遗传时钟通常是物种特有的,但支撑它们的原理似乎至少在哺乳动物类别中是保守的。老鼠和其他几种哺乳动物的表观遗传时钟的成功开发就是一个例证。在这里,我们描述了恒河猴(猕猴)的表观遗传学时钟,猕猴是生物学研究中使用最广泛的非人类灵长类动物。使用一个定制的甲基化阵列(HorvathMamMalMethylChip40),我们分析了n个 = 281个组织样本(血液、皮肤、脂肪、肾脏、肝脏、肺、肌肉和大脑皮层)。从这些数据中,我们为猕猴产生了五个表观遗传学时钟。这些时钟在不同的组织类型(泛组织、血液、皮肤)、物种(仅限于猕猴或人类和猕猴都适用)以及年龄测量(按时间顺序计算的年龄与相对年龄)方面有所不同。此外,基于年龄的人类-猕猴时钟显示出与另一个东半球物种--扁尾猴(ChlorOcean Bus Sabaeus)高度相关的年龄相关性(R = 0.89)。KLF14启动子内的四个CPGS在四个组织(脂肪、血液、大脑皮层、皮肤)中随着年龄的增长而持续变化。未来的研究将需要评估这些表观遗传学时钟是否可以预测恒河猴的年龄相关疾病。网上版载有补充材料,可在10.1007/s11357.021-00429-8查阅。
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. The online version contains supplementary material available at 10.1007/s11357-021-00429-8.
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