Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing.
Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing.
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小鼠肝脏中DNA双链断裂的受控诱导会诱导组织衰老的特征。
DOI：
10.1038/ncomms7790
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发表时间：
2015-04-10
影响因子：
16.6
通讯作者：
Vijg, Jan
中科院分区：
文献类型：
--
作者：
White, Ryan R.;Milholland, Brandon;de Bruin, Alain;Curran, Samuel;Laberge, Remi-Martin;van Steeg, Harry;Campisi, Judith;Maslov, Alexander Y.;Vijg, Jan
DNA损伤与衰老有关，但缺乏因果关系的直接证据，因为很难在细胞和组织中诱导明确的DNA损伤而不同时损害其他生物分子和细胞结构。在这里，我们直接测试是否高毒性的DNA双链断裂（DSB）单独使用基于四环素控制的SacI限制性内切酶表达的腺病毒系统可以驱动衰老表型。我们将腺病毒传递给小鼠，并将肝脏中的分子和细胞终点与正常年龄的动物进行比较。经治疗的3个月大的小鼠早在治疗后1个月就显示出许多但不是所有的正常肝脏衰老迹象，包括衰老病理学、衰老标志物、融合的线粒体和基因表达谱的改变。这些结果表明，DSB单独可以在小鼠肝脏中引起不同的衰老表型，为DNA损伤作为组织衰老驱动因素的作用提供了新的见解。 DNA损伤的累积是细胞衰老的标志，但因果关系尚不清楚。在这里，白色等人使用改良的限制性内切酶在小鼠肝脏中诱导干净的DNA双链断裂，并证明单独的DNA损伤足以重现组织老化的某些方面。
DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing. Accumulation of DNA damage is a hallmark of cellular ageing but cause and effect are unclear. Here White et al. induce clean DNA double-strand breaks in the liver of mice using a modified restriction enzyme and demonstrate that DNA damage alone is sufficient to recapitulate some aspects of tissue ageing.
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影响因子：
21.3
作者：
Jones, D. Leanne;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
DOI：
10.1093/gerona/glt169
发表时间：
2014-09-01
影响因子：
5.1
作者：
Cogger, Victoria C.;Svistounov, Dmitri;Lebel, Michel
通讯作者：
Lebel, Michel
影响因子：
3.6
作者：
Ding, GH;Franki, N;Singhal, PC
通讯作者：
Singhal, PC
影响因子：
3.5
作者：
Faggioli, Francesca;Wang, Tao;Montagna, Cristina
通讯作者：
Montagna, Cristina
影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars