Cross-talk between aging and cancer - The epigenetic language
Cross-talk between aging and cancer - The epigenetic language
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DOI：
10.1196/annals.1395.005
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Esteller, Manel
中科院分区：
文献类型：
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作者：
Fraga, Mario F.;Agrelo, Ruben;Esteller, Manel
患癌症的风险随着年龄的增长而增加，这可能是因为来自成熟生物体的祖细胞积累了足够的分子损伤，以逃避其组织环境的稳态控制。分子病变可以是遗传的（突变、缺失或易位）和/或表观遗传的。表观遗传信号，包括DNA甲基化和组蛋白修饰，是正常发育所必需的，并在衰老和癌症期间发生改变。一些表观遗传改变，如整体低甲基化和CpG岛高甲基化，在衰老过程中逐渐积累，并直接促进细胞转化。有趣的是，其他的，如参与控制端粒长度的那些和属于烟酰胺腺嘌呤二核苷酸（NAD）（+）依赖性脱乙酰酶家族的几种表观遗传酶，称为sirtuins，在衰老过程中表现出明确的进展，在转化细胞中急剧逆转。我们讨论了这两组表观遗传修饰的生物学意义方面的相对贡献个体发育，衰老和细胞增殖。
The risk of having cancer increases with age probably because progenitor cells from mature organisms accumulate enough molecular lesions to evade the homeostatic control of their tissular contexts. Molecular lesions can be genetic (mutations, deletions, or translocations) and/or epigenetic. Epigenetic signaling, including DNA methylation and histone modification, is essential for normal development and becomes altered during Aging and by cancer. Several epigenetic alterations, such as global hypomethylation and CpG island hypermethylation, are progressively accumulated during Aging and directly contribute to cell transformation. Intriguingly, others, such as those involved in the control of telomere length and several epigenetic enzymes belonging to the family of nicotinamide adenine dinucleotide (NAD)(+) dependent deacetylases known as sirtuins, exhibit a well-defined progression during Aging that is dramatically reverted in transformed cells. We discuss the biological significance of both groups of epigenetic modifications in terms of their relative contribution to ontogenic development, senescence, and cell proliferation.