Epigenome-wide analysis of aging effects on liver regeneration.
Epigenome-wide analysis of aging effects on liver regeneration.
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DOI：
10.1186/s12915-023-01533-1
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发表时间：
2023-02-13
期刊：
影响因子：
5.4
通讯作者：
Tsai, Robert Y. L.
中科院分区：
文献类型：
--
作者：
Wang, Junying;Zhang, Wen;Liu, Xiaoqin;Kim, Minjee;Zhang, Ke;Tsai, Robert Y. L.
众所周知，衰老会对肝脏再生产生影响，随着时间的推移，肝脏再生的能力会显著下降。在人类和模型系统中，肝脏的生理参数，如肝脏体积、血流和新陈代谢，以及损伤后再生的能力，都被证明在老年时都会下降，可能涉及许多分子机制，包括DNA甲基化依赖的基因组重塑。为了阐明DNA甲基化的变化如何介导衰老对肝脏再生的不利影响，我们在小鼠肝脏中寻找受衰老和再生共同调节的差异甲基化基因组区域(DMRS)，并确定了它们的相关基因和丰富的途径。用全基因组亚硫酸氢盐测序(WGBS)鉴定DMR。对DMR定位的衰老基因的路径分析显示了两个不同的衰老阶段，2到8个月大和8到16个月大(m/o)。再生DMR定位的差异表达基因(DEG)丰富了控制细胞增殖和分化的途径。老化和再生所共有的DMR大多在2~8 Mm/o之间以相同的甲基化方向变化，而在8~16 Cm/o之间则相反。在8~16 Cm/o期间，12个基因的启动子/基因区发现了受老化相反影响的再生性DMR。4个再生DEG受早期衰老的同步调节，受中晚期衰老的DMR的反向调节。铅DMR定位的基因通过它们在肝脏老化和再生中的表达谱得到验证。我们的研究发现了新的DMR和受肝脏老化和再生相反影响的基因靶点，以解释衰老对肝脏再生的不利影响。这些发现对于理解衰老对肝脏再生生物学基础的表观基因组学变化具有重要意义。网上版载有补充材料，可在10.1186/s12915-023-01533-1查阅。
Aging is known to exert an effect on liver regeneration, with the ability of liver to regenerate displaying a significant decline over time. Liver physiological parameters such as liver volume, blood flow, and metabolism, as well as the ability to regenerate after injury have all been shown to decrease at old age in humans and model systems, with a number of molecular mechanisms proposed to be involved, including DNA methylation-dependent genome remodeling. To address how changes in DNA methylation mediate the adverse aging effect on liver regeneration, we searched for differentially methylated genomic regions (DMRs) in mouse livers co-regulated by aging and regeneration and determined their associated genes and enriched pathways. DMRs were identified using whole-genome bisulfite sequencing (WGBS). Pathway analysis of aging DMR-mapped genes revealed two distinct phases of aging, 2-to-8 and 8-to-16 months old (m/o). Regenerative DMR-mapped differentially expressed genes (DEGs) were enriched in pathways controlling cell proliferation and differentiation. Most DMRs shared by both aging and regeneration changed in the same methylation direction between 2 and 8 m/o but in the opposite direction between 8 and 16 m/o. Regenerative DMRs inversely affected by aging during 8-to-16 m/o were found in the promoter/gene regions of 12 genes. Four regenerative DEGs were synchronously regulated by early aging and inversely regulated by mid-to-late aging DMRs. Lead DMR-mapped genes were validated by their expression profiles in liver aging and regeneration. Our study has uncovered new DMRs and gene targets inversely affected by liver aging and regeneration to explain the adverse aging effect on liver regeneration. These findings will be of fundamental importance to understand the epigenomic changes underlying the biology of aging on liver regeneration. The online version contains supplementary material available at 10.1186/s12915-023-01533-1.
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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
DOI：
10.1196/annals.1395.005
发表时间：
2007-01-01
期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
--
作者：
Fraga, Mario F.;Agrelo, Ruben;Esteller, Manel
通讯作者：
Esteller, Manel
DOI：
10.18632/aging.100060
发表时间：
2009-06-22
期刊：
Aging
影响因子：
--
作者：
Jin J;Wang GL;Timchenko L;Timchenko NA
通讯作者：
Timchenko NA
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
13.5
作者：
Jin, Jingling;Iakova, Polina;Jiang, Yanjun;Medrano, Estela E.;Timchenko, Nikolai A.
通讯作者：
Timchenko, Nikolai A.