Underlying features of epigenetic aging clocks in vivo and in vitro.
Underlying features of epigenetic aging clocks in vivo and in vitro.
复制标题
DOI：
10.1111/acel.13229
复制
发表时间：
2020-10
期刊：
影响因子：
7.8
通讯作者：
Levine ME
中科院分区：
文献类型：
--
作者：
Liu Z;Leung D;Thrush K;Zhao W;Ratliff S;Tanaka T;Schmitz LL;Smith JA;Ferrucci L;Levine ME
利用DNA甲基化数据开发的表观遗传时钟已被广泛用于量化多种组织/细胞中的生物衰老。然而，许多现有的表观遗传时钟彼此之间的相关性很弱，这表明它们可能捕获不同的生物过程。我们利用来自不同人类组织/细胞的多组学数据来识别11个现有表观遗传时钟的共享特征。尽管CpG序列明显缺乏重叠，但多组学分析表明，五个时钟（Horvath 1，Horvath 2，Levine，Hannum和Lin）在纯化的CD 14+单核细胞和背外侧前额叶皮层中共享保守的转录关联。在共享的转录关联中富集的途径表明表观遗传衰老与代谢、免疫和自噬之间的联系。体外实验的结果表明，两个时钟（莱文和林）加速与衰老的两个标志细胞衰老和线粒体功能障碍。最后，使用多组织数据来解构表观遗传时钟信号，我们开发了一种Meta时钟，与单个时钟相比，该元时钟显示出对死亡率的预测得到了改善，并且与体外衰老的标志密切相关。我们比较了11个现有的表观遗传时钟的基础上，他们的功能特征，转录协会，并捕捉衰老的标志的能力。然后我们分解它们的信号并将它们重新组合成一个“Meta时钟”。这种Meta时钟显示出比任何一种表观遗传时钟更强的全因死亡率预测能力，并且能够区分肿瘤和正常组织，并捕获两种类型衰老（复制型和癌基因诱导型）的表观遗传变化。
Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi‐omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi‐omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging—cellular senescence and mitochondrial dysfunction. Finally, using multi‐tissue data to deconstruct the epigenetic clock signals, we developed a meta‐clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks. We compared 11 existing epigenetic clocks on the basis of their functional characteristics, transcriptional associations, and ability to capture hallmarks of aging. We then decomposed their signals and recombined them into a “meta‐clock.” This meta‐clock showed stronger prediction of all‐cause mortality than any one epigenetic clock and was able to distinguish tumor from normal tissue and capture epigenetic changes in two types of senescence (replicative and oncogene induced).
登录
查看更多内容
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
表观遗传有丝分裂时钟与癌症风险的相关性
影响因子：
12.3
作者：
Yang Z;Wong A;Kuh D;Paul DS;Rakyan VK;Leslie RD;Zheng SC;Widschwendter M;Beck S;Teschendorff AE
通讯作者：
Teschendorff AE
影响因子：
56.9
作者：
ROCKSTEIN, M;BRANDT, KF
通讯作者：
BRANDT, KF
DOI：
10.18632/aging.101414
发表时间：
2018-04-18
期刊：
Aging
影响因子：
--
作者：
Levine ME;Lu AT;Quach A;Chen BH;Assimes TL;Bandinelli S;Hou L;Baccarelli AA;Stewart JD;Li Y;Whitsel EA;Wilson JG;Reiner AP;Aviv A;Lohman K;Liu Y;Ferrucci L;Horvath S
通讯作者：
Horvath S
影响因子：
3.5
作者：
Florath, Ines;Butterbach, Katja;Brenner, Hermann
通讯作者：
Brenner, Hermann