Gorbunova Vera, Seluanov Andrei
University of Rochester, Department of Biology, Hutchison Hall, RC, Rochester, NY 14627, USA.
University of Rochester, Department of Biology, Hutchison Hall, RC, Rochester, NY 14627, USA.
Mutat Res. 2016 Jun;788:2-6. doi: 10.1016/j.mrfmmm.2016.02.004. Epub 2016 Feb 15.
Are DNA damage and mutations possible causes or consequences of aging? This question has been hotly debated by biogerontologists for decades. The importance of DNA damage as a possible driver of the aging process went from being widely recognized to then forgotten, and is now slowly making a comeback. DNA double strand breaks (DSBs) are particularly relevant to aging because of their toxicity, increased frequency with age and the association of defects in their repair with premature aging. Recent studies expand the potential impact of DNA damage and mutations on aging by linking DNA DSB repair and age-related chromatin changes. There is overwhelming evidence that increased DNA damage and mutations accelerate aging. However, an ultimate proof of causality would be to show that enhanced genome and epigenome stability delays aging. This is not an easy task, as improving such complex biological processes is infinitely more difficult than disabling it. We will discuss the possibility that animal models with enhanced DNA repair and epigenome maintenance will be generated in the near future.
DNA损伤和突变是衰老的可能原因还是后果？几十年来，这个问题一直是生物老年学家激烈争论的焦点。DNA损伤作为衰老过程的一个可能驱动因素，其重要性从被广泛认可到后来被遗忘，而现在又在慢慢卷土重来。DNA双链断裂（DSB）与衰老特别相关，因为它们具有毒性，随着年龄增长频率增加，且其修复缺陷与早衰有关。最近的研究通过将DNA DSB修复与年龄相关的染色质变化联系起来，扩展了DNA损伤和突变对衰老的潜在影响。有压倒性的证据表明，DNA损伤和突变增加会加速衰老。然而，因果关系的最终证明将是表明增强的基因组和表观基因组稳定性会延缓衰老。这并非易事，因为改善如此复杂的生物过程比使其失效要困难得多。我们将讨论在不久的将来生成具有增强DNA修复和表观基因组维持能力的动物模型的可能性。
