Abstract

In the last ten years, the discovery of neuronal DNA postmitotic instability has changed the theoretical landscape in neuroscience and, more broadly, biology. In 2003, A. M. Olovnikov suggested that neuronal DNA is the “initial substrate of aging”. Recent experimental data have significantly increased the likelihood of this hypothesis. How does neuronal DNA accumulate damage and in what genome regions? What factors contribute to this process and how are they associated with aging and lifespan? These questions will be discussed in the review. In the course of Metazoan evolution, the instability of neuronal DNA has been accompanied by searching for the pathways to reduce the biological cost of brain activity. Various processes and activities, such as sleep, evolutionary increase in the number of neurons in the vertebrate brain, adult neurogenesis, distribution of neuronal activity, somatic polyploidy, and RNA editing in cephalopods, can be reconsidered in the light of the trade-off between neuronal plasticity and DNA instability in neurons. This topic is of considerable importance for both fundamental neuroscience and translational medicine.

中文翻译：

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神经元中的 DNA 不稳定性：寿命时钟和进化驱动力

摘要

在过去十年中，神经元 DNA 有丝分裂后不稳定性的发现改变了神经科学乃至更广泛的生物学的理论格局。2003年，A. M. Olovnikov提出神经元DNA是“衰老的最初基质”。最近的实验数据显着增加了这一假设的可能性。神经元 DNA 如何累积损伤以及在哪些基因组区域？哪些因素促成了这一过程？它们与衰老和寿命有何关系？这些问题将在审查中讨论。在后生动物的进化过程中，神经元DNA的不稳定性一直伴随着寻找降低大脑活动的生物成本的途径。各种过程和活动，例如睡眠、脊椎动物大脑中神经元数量的进化增加、成体神经发生、神经元活动的分布、体细胞多倍体和头足类动物的 RNA 编辑，可以根据之间的权衡重新考虑神经元可塑性和神经元 DNA 不稳定性。这个主题对于基础神经科学和转化医学都非常重要。