Wagner Wolfgang
Division of Stem Cell Biology and Cellular Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
Institute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Front Genet. 2019 Apr 3;10:303. doi: 10.3389/fgene.2019.00303. eCollection 2019.
Replicative senescence of cells is often considered as counterpart for aging of the organism . In fact, both processes are associated with functional decay and similar molecular modifications. On epigenetic level, replicative senescence and aging evoke characteristic modifications in the DNA methylation (DNAm) pattern, but at different sites in the genome. Various epigenetic signatures, which are often referred to as epigenetic clocks, provide useful biomarkers: Senescence-associated epigenetic modifications can be used for quality control of cell preparations or to elucidate effects of culture conditions on the state of cellular aging. Age-associated epigenetic modifications hold high expectations to determine chronological age in forensics or to identify parameters that impact on biological aging. Despite these differences, there are some striking similarities between senescence- and age-associated DNAm, such as complete rejuvenation during reprogramming into induced pluripotent stem cells (iPSCs). It is yet unclear what makes epigenetic clocks tick, but there is evidence that the underlying mechanisms of both processes are related to similar modifications in the histone code or higher order chromatin. Replicative senescence therefore appears to be a suitable model system to gain better insight into how organismal aging might be governed epigenetically.
细胞的复制性衰老通常被视为生物体衰老的对应过程。事实上，这两个过程都与功能衰退和相似的分子修饰有关。在表观遗传水平上，复制性衰老和衰老会在DNA甲基化（DNAm）模式中引发特征性修饰，但发生在基因组的不同位点。各种表观遗传特征，通常被称为表观遗传时钟，提供了有用的生物标志物：与衰老相关的表观遗传修饰可用于细胞制剂的质量控制，或阐明培养条件对细胞衰老状态的影响。与年龄相关的表观遗传修饰在法医学中确定实际年龄或识别影响生物衰老的参数方面寄予厚望。尽管存在这些差异，但与衰老和年龄相关的DNAm之间仍有一些惊人的相似之处，比如重编程为诱导多能干细胞（iPSC）过程中的完全年轻化。目前尚不清楚是什么驱动表观遗传时钟，但有证据表明这两个过程的潜在机制与组蛋白密码或高阶染色质中的相似修饰有关。因此，复制性衰老似乎是一个合适的模型系统，有助于更好地了解生物体衰老可能如何受表观遗传调控。
