当前位置: X-MOL 学术Geroscience › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Epigenetic clock and methylation studies in vervet monkeys
GeroScience ( IF 5.3 ) Pub Date : 2021-09-30 , DOI: 10.1007/s11357-021-00466-3
Anna J Jasinska 1, 2, 3 , Amin Haghani 4 , Joseph A Zoller 5 , Caesar Z Li 5 , Adriana Arneson 6, 7 , Jason Ernst 6, 7 , Kylie Kavanagh 8, 9 , Matthew J Jorgensen 8 , Julie A Mattison 10 , Kevin Wojta 1, 11 , Oi-Wa Choi 1 , Joseph DeYoung 1 , Xinmin Li 12 , Andrew W Rao 12 , Giovanni Coppola 1, 11 , Nelson B Freimer 1, 4 , Roger P Woods 1, 11 , Steve Horvath 4, 5
Affiliation  

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.



中文翻译:

长尾猴的表观遗传时钟和甲基化研究

已经为许多哺乳动物开发了基于 DNA 甲基化的衰老生物标志物,但尚未为黑长尾猴(Chlorocebus sabaeus), 这是一种有价值的非人灵长类动物模型,可用于生物医学研究。我们使用定制阵列 (HorvathMammalMethylChip40) 上代表的高度保守的哺乳动物 CpG,从黑长尾动物大脑皮层、血液和肝脏生成了新的 DNA 甲基化数据。我们提出了六个基于 DNA 甲基化的年龄估计器:黑长尾动物多组织表观遗传时钟和大脑皮层、血液和肝脏的组织特异性时钟。此外,我们开发了两个双物种时钟(人类黑猩猩时钟),分别用于测量实足年龄和相对年龄。相对年龄被定义为实际年龄与最大寿命的比率,以解决最大寿命的物种差异。人黑猩猩时钟的高精度表明表观遗传衰老过程在灵长类动物中是进化保守的。当将这些黑长尾动物时钟应用于另一种灵长类动物恒河猴的组织样本时,我们观察到年龄相关性高但偏移量大。我们对黑长尾动物中与年龄显着相关的 CpG 进行了表征。随着年龄的增长跨组织获得甲基化的 CpG 探针位于 Polycomb 蛋白 SUZ12 和 EED 的靶标附近,以及在其启动子中具有三甲基化 H3K27 标记的基因。表观遗传时钟有望用于黑长尾动物的抗衰老研究。随着年龄的增长跨组织获得甲基化的 CpG 探针位于 Polycomb 蛋白 SUZ12 和 EED 的靶标附近,以及在其启动子中具有三甲基化 H3K27 标记的基因。表观遗传时钟有望用于黑长尾动物的抗衰老研究。随着年龄的增长跨组织获得甲基化的 CpG 探针位于 Polycomb 蛋白 SUZ12 和 EED 的靶标附近,以及在其启动子中具有三甲基化 H3K27 标记的基因。表观遗传时钟有望用于黑长尾动物的抗衰老研究。

更新日期:2021-09-30
down
wechat
bug