Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain. As in neurons, unrepaired DNA damage accumulates in the postmitotic oligodendrocyte genome during normal aging, and indeed may be one of the upstream causes of cellular aging - a fact well illustrated by myelin co-morbidity in premature aging syndromes arising from deficits in DNA repair enzymes. The clinical and experimental evidence from Alzheimer's disease, progeroid syndromes, ataxia-telangiectasia and other conditions strongly suggest that oligodendrocytes may in fact be uniquely vulnerable to oxidative DNA damage. If this damage remains unrepaired, as is increasingly true in the aging brain, myelin gene transcription and oligodendrocyte differentiation is impaired. Delineating the relationships between early myelin loss and DNA damage in brain aging will offer an additional dimension outside the neurocentric view of neurodegenerative disease.

中文翻译：

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少突胶质细胞谱系中的DNA损伤及其在脑衰老中的作用。

髓鞘化是近来的进化添加物，其显着提高了神经网络中的传输速度。髓磷脂完整性的轻微缺陷也会损害性能，并增加神经系统疾病的风险。确实，髓磷脂变性是一种早期且公认的神经病理学，与年龄有关，但出现在认知能力下降之前。髓磷脂仅由完全分化的少突胶质细胞形成，但整个少突胶质细胞谱系是衰老大脑化学性质改变的明确靶标。与神经元一样，未修复的DNA损伤会在正常衰老过程中累积在有丝分裂后少突胶质细胞基因组中，并且确实可能​​是细胞衰老的上游原因之一-由DNA修复酶缺陷引起的过早衰老综合征中的髓磷脂合并症已充分说明了这一事实。 。来自阿尔茨海默氏病，早衰综合症，共济失调-毛细血管扩张和其他疾病的临床和实验证据强烈表明，少突胶质细胞实际上可能是唯一易受氧化性DNA损伤的。如果这种损害没有得到修复，就像在衰老的大脑中一样，那么髓磷脂基因的转录和少突胶质细胞的分化就会受到损害。描绘早期髓磷脂损失与脑衰老中的DNA损伤之间的关系将为神经退行性疾病的以神经为中心的观点提供一个新的维度。髓磷脂基因转录和少突胶质细胞分化受损。描绘早期髓磷脂损失与脑衰老中的DNA损伤之间的关系将为神经退行性疾病的以神经为中心的观点提供一个新的维度。髓磷脂基因转录和少突胶质细胞分化受损。描绘早期髓磷脂损失与脑衰老中的DNA损伤之间的关系将为神经退行性疾病的以神经为中心的观点提供一个新的维度。