Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction.
Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction.
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DOI：
10.1111/acel.12738
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发表时间：
2018-06
期刊：
影响因子：
7.8
通讯作者：
Gladyshev VN
中科院分区：
文献类型：
--
作者：
Sziráki A;Tyshkovskiy A;Gladyshev VN
衰老的特征是许多分子变化，如分子损伤的积累和基因表达的改变，其中许多与DNA甲基化有关。在这里，我们描述了16个年龄组小鼠的血液DNA甲基化组，并报告了许多全球，区域和位点特异性特征，以及甲基化变化的相关动态。整个生命周期中甲基化组的转变并不均匀，许多位点在晚年显示出加速变化。相关的基因和启动子富集了衰老相关的途径，指出了DNA甲基化和衰老过程控制之间的基本联系。热量限制改变了整体甲基化模式，并伴随着其逐渐的年龄相关重塑，后者有助于延长寿命。随着年龄的增长，高度甲基化和低度甲基化的位点都趋向于中间水平，并且老化伴随着熵的加速增加，与损伤积累一致。然而，熵效应不同的网站，增加，减少，并没有改变甲基化随着年龄的增长。许多位点落后，而有些位点遵循甚至超过熵轨迹，并改变了发育DNA甲基化模式。我们在某些基因组区域观察到的模式在人类和小鼠之间是保守的，这表明了功能性DNA甲基化重塑的共同原则及其在衰老中的关键作用。高分辨率的DNA甲基化重构为理解表征衰老过程的系统性变化提供了一个很好的模型。
Aging is characterized by numerous molecular changes, such as accumulation of molecular damage and altered gene expression, many of which are linked to DNA methylation. Here, we characterize the blood DNA methylome across 16 age groups of mice and report numerous global, region‐ and site‐specific features, as well as the associated dynamics of methylation changes. Transition of the methylome throughout lifespan was not uniform, with many sites showing accelerated changes in late life. The associated genes and promoters were enriched for aging‐related pathways, pointing to a fundamental link between DNA methylation and control of the aging process. Calorie restriction both shifted the overall methylation pattern and was accompanied by its gradual age‐related remodeling, the latter contributing to the lifespan‐extending effect. With age, both highly and poorly methylated sites trended toward intermediate levels, and aging was accompanied by an accelerated increase in entropy, consistent with damage accumulation. However, the entropy effects differed for the sites that increased, decreased and did not change methylation with age. Many sites trailed behind, whereas some followed or even exceeded the entropy trajectory and altered the developmental DNA methylation pattern. The patterns we observed in certain genomic regions were conserved between humans and mice, suggesting common principles of functional DNA methylome remodeling and its critical role in aging. The highly resolved DNA methylome remodeling provides an excellent model for understanding systemic changes that characterize the aging process.
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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：
3.1
作者：
Ott, Christiane;Grune, Tilman
通讯作者：
Grune, Tilman
影响因子：
8
作者：
Lujambio, A.;Portela, A.;Liz, J.;Melo, S. A.;Rossi, S.;Spizzo, R.;Croce, C. M.;Calin, G. A.;Esteller, M.
通讯作者：
Esteller, M.
影响因子：
7.8
作者：
Harrison DE;Strong R;Allison DB;Ames BN;Astle CM;Atamna H;Fernandez E;Flurkey K;Javors MA;Nadon NL;Nelson JF;Pletcher S;Simpkins JW;Smith D;Wilkinson JE;Miller RA
通讯作者：
Miller RA
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