Aging is associated with a progressive decline of brain function, and the underlying causes and possible interventions to prevent this cognitive decline have been the focus of intense investigation. The maintenance of neuronal function over the lifespan requires proper epigenetic regulation, and accumulating evidence suggests that the deterioration of the neuronal epigenetic landscape contributes to brain dysfunction during aging. Epigenetic aging of neurons may, however, be malleable. Recent reports have shown age-related epigenetic changes in neurons to be reversible and targetable by rejuvenation strategies that can restore brain function during aging. This review discusses the current evidence that identifies neuronal epigenetic aging as a driver of cognitive decline and a promising target of brain rejuvenation strategies, and it highlights potential approaches for the specific manipulation of the aging neuronal epigenome to restore a youthful epigenetic state in the brain.

中文翻译：

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靶向神经元表观基因组以实现大脑年轻化。


衰老与大脑功能的逐渐衰退有关，其根本原因和预防这种认知衰退的可能干预措施一直是深入研究的焦点。在整个生命周期中神经元功能的维持需要适当的表观遗传调节，并且越来越多的证据表明神经元表观遗传景观的恶化会导致衰老过程中的大脑功能障碍。然而，神经元的表观遗传衰老可能是可塑的。最近的报告表明，神经元中与年龄相关的表观遗传变化是可逆的，并且可以通过恢复衰老策略来恢复大脑功能。这篇综述讨论了当前的证据，这些证据表明神经元表观遗传衰老是认知能力下降的一个驱动因素，也是大脑年轻化策略的一个有希望的目标，并强调了对衰老的神经元表观基因组进行特定操作以恢复大脑年轻表观遗传状态的潜在方法。