Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer.
Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer.
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DOI：
10.1016/j.stem.2015.05.002
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发表时间：
2015-06-04
期刊：
影响因子：
23.9
通讯作者：
Rudolph KL
中科院分区：
文献类型：
--
作者：
Adams PD;Jasper H;Rudolph KL
衰老的特点是基因组完整性下降、器官维护受损和癌症风险增加，这与衰老组织（如肠上皮、造血系统和雄性生殖系）中扩大的突变干细胞和祖细胞群的克隆优势相一致。在这里，我们讨论了突变干细胞/祖细胞克隆的起始和/或进展与年龄相关的增加的可能解释，并强调了干细胞静止、复制相关的DNA损伤、端粒缩短、表观遗传改变和代谢挑战作为干细胞突变和克隆优势在衰老中的决定因素的作用。在这篇综述中，Rudolph 及其同事讨论了突变干细胞/祖细胞克隆的起始和/或进展与年龄相关的增加，以及干细胞静止、复制相关的 DNA 损伤、端粒缩短、表观遗传改变和代谢挑战作为干细胞突变和克隆优势在衰老中的决定因素的作用。
Aging is characterized by a decrease in genome integrity, impaired organ maintenance, and an increased risk of cancer, which coincide with clonal dominance of expanded mutant stem and progenitor cell populations in aging tissues, such as the intestinal epithelium, the hematopoietic system, and the male germline. Here we discuss possible explanations for age-associated increases in the initiation and/or progression of mutant stem/progenitor clones and highlight the roles of stem cell quiescence, replication-associated DNA damage, telomere shortening, epigenetic alterations, and metabolic challenges as determinants of stem cell mutations and clonal dominance in aging. In this review, Rudolph and colleagues discuss age-associated increases in the initiation and/or progression of mutant stem/progenitor clones and the roles of stem cell quiescence, replication-associated DNA damage, telomere shortening, epigenetic alterations, and metabolic challenges as determinants of stem cell mutations and clonal dominance in aging.