DNA methylation entropy as a measure of stem cell replication and aging.
DNA methylation entropy as a measure of stem cell replication and aging.
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DOI：
10.1186/s13059-023-02866-4
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发表时间：
2023-02-16
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
--
作者：
表观遗传标记由DNA甲基化编码，并随着生物体年龄的增长而积累错误。这种漂移与寿命相关，但这种漂移如何发生的生物学仍然无法解释。我们分析了小鼠肠道干细胞中DNA甲基化与年龄的关系，并将其与非干细胞进行了比较。干细胞和非干细胞的DNA甲基化中与CpG岛相关的变化是相同的，最显著地影响CpG岛，并且与基因表达弱相关。通过詹森-香农分布测量的与衰老相关的DNA甲基化熵影响高达25%的可检测CpG位点，并且是比单个CpG甲基化更好的衰老度量。我们分析了其他七种组织（心脏、肾脏、骨骼肌、肺、肝脏、脾脏和血液）的熵随年龄的变化，它与组织特异性干细胞分裂率显著相关。因此，DNA甲基化漂移和熵随年龄的增加主要是由成人组织中的干细胞复制引起的，并且是干细胞复制的传感器。这些数据对组织特异性功能随衰老而下降的机制和基于DNA甲基化的生物钟的发展具有影响。 在线版本包含补充材料，可通过10.1186/s13059-023-02866-4获得。
Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells. Age-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. These data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks. The online version contains supplementary material available at 10.1186/s13059-023-02866-4.
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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
影响因子：
16.6
作者：
Aran D;Camarda R;Odegaard J;Paik H;Oskotsky B;Krings G;Goga A;Sirota M;Butte AJ
通讯作者：
Butte AJ
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：
30.8
作者：
Landan, Gilad;Cohen, Netta Mendelson;Tanay, Amos
通讯作者：
Tanay, Amos
影响因子：
13.6
作者：
Pal S;Tyler JK
通讯作者：
Tyler JK