Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer's disease.
Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer's disease.
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海马和皮质组织特异性表观遗传钟表明，阿尔茨海默氏病小鼠模型中的表观遗传年龄增加。
DOI：
10.18632/aging.104056
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发表时间：
2020-10-20
期刊：
影响因子：
--
通讯作者：
Quintens R
中科院分区：
文献类型：
--
作者：
Coninx E;Chew YC;Yang X;Guo W;Coolkens A;Baatout S;Moons L;Verslegers M;Quintens R
表观遗传时钟是基于CpG位点DNA甲基化的年龄相关变化，可以准确地测量不同物种的时间年龄。最近，一些研究表明，时间年龄和表观遗传年龄之间的差异，定义为年龄加速，可以反映指示功能衰退的生物学年龄和年龄相关疾病。在人类中，表观遗传时钟将阿尔茨海默病(AD)的病理与表观遗传年龄的加速联系在一起。在这项研究中，我们从C57BL/6J海马区和大脑皮层开发并验证了两个小鼠大脑区域特定的表观遗传学时钟。这两个时钟都可以成功地估计出年龄，并在一个广泛使用的AD小鼠模型--三重转基因AD(3xTg-AD)小鼠模型上得到了进一步的验证。我们观察到表观遗传年龄加速，表明3xTg-AD小鼠与非病理性C57BL/6J小鼠相比，生物年龄增加，这在皮质比海马区更明显。基因组区域富集区分析表明，与年龄相关的CPGS富含与发育、衰老相关、神经元和神经退行性功能相关的基因。由于人类脑组织的可获得性有限，这些针对小鼠皮质和海马区的表观遗传时钟可能对于进一步揭示AD病理或脑老化的表观遗传机制的作用具有重要意义。
Epigenetic clocks are based on age-associated changes in DNA methylation of CpG-sites, which can accurately measure chronological age in different species. Recently, several studies have indicated that the difference between chronological and epigenetic age, defined as the age acceleration, could reflect biological age indicating functional decline and age-associated diseases. In humans, an epigenetic clock associated Alzheimer’s disease (AD) pathology with an acceleration of the epigenetic age. In this study, we developed and validated two mouse brain region-specific epigenetic clocks from the C57BL/6J hippocampus and cerebral cortex. Both clocks, which could successfully estimate chronological age, were further validated in a widely used mouse model for AD, the triple transgenic AD (3xTg-AD) mouse. We observed an epigenetic age acceleration indicating an increased biological age for the 3xTg-AD mice compared to non-pathological C57BL/6J mice, which was more pronounced in the cortex as compared to the hippocampus. Genomic region enrichment analysis revealed that age-dependent CpGs were enriched in genes related to developmental, aging-related, neuronal and neurodegenerative functions. Due to the limited access of human brain tissues, these epigenetic clocks specific for mouse cortex and hippocampus might be important in further unravelling the role of epigenetic mechanisms underlying AD pathology or brain aging in general.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
影响因子：
6.1
作者：
Detrez, Jan R.;Maurin, Herve;De Vos, Winnok H.
通讯作者：
De Vos, Winnok H.
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Delgado-Morales R;Agís-Balboa RC;Esteller M;Berdasco M
通讯作者：
Berdasco M