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Epigenetic clock and methylation studies in elephants
Aging Cell ( IF 8.0 ) Pub Date : 2021-06-12 , DOI: 10.1111/acel.13414
Natalia A Prado 1, 2 , Janine L Brown 1 , Joseph A Zoller 3 , Amin Haghani 4 , Mingjia Yao 3 , Lora R Bagryanova 5 , Michael G Campana 2 , Jesús E Maldonado 2 , Ken Raj 6 , Dennis Schmitt 7 , Todd R Robeck 8 , Steve Horvath 3, 4
Affiliation  

Age-associated DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We present epigenetic clocks for Asian elephants (Elephas maximus), African elephants (Loxodonta africana), and both elephant species combined. Two additional human-elephant clocks were constructed by combining human and elephant samples. Epigenome-wide association studies identified elephant age-related CpGs and their proximal genes. The products of these genes play important roles in cellular differentiation, organismal development, metabolism, and circadian rhythms. Intracellular events observed to change with age included the methylation of bivalent chromatin domains, and targets of polycomb repressive complexes. These readily available epigenetic clocks can be used for elephant conservation efforts where accurate estimates of age are needed to predict demographic trends.

中文翻译:


大象的表观遗传时钟和甲基化研究



与年龄相关的 DNA 甲基化谱已成功用于在人类、小鼠、狗和其他物种中开发高度准确的年龄生物标志物(“表观遗传时钟”)。在这里,我们展示了非洲象和亚洲象的表观遗传时钟。这些时钟是使用定制的 Infinium 阵列 (HorvathMammalMmethylChip40),利用 140 个已知年龄的大象血液样本的新颖 DNA 甲基化图谱开发的,这些样本位于哺乳动物物种之间高度保守的位点。我们展示了亚洲象( Elephas maximus )、非洲象( Loxodonta africana )以及两种大象的表观遗传时钟。另外两个人象时钟是通过结合人类和大象样本建造的。表观基因组范围的关联研究确定了与大象年龄相关的 CpG 及其近端基因。这些基因的产物在细胞分化、有机体发育、新陈代谢和昼夜节律中发挥重要作用。观察到随年龄变化的细胞内事件包括二价染色质结构域的甲基化和多梳抑制复合物的靶标。这些现成的表观遗传时钟可用于大象保护工作,其中需要准确估计年龄来预测人口趋势。
更新日期:2021-07-16
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