Post-translational epigenetic modifications take place in mouse neurons of the dentate gyrus (DG) with age. Here, we report that age-dependent reduction in H3K9 trimethylation (H3K9me3) is prevented by cyclic induction of the Yamanaka factors used for cell reprogramming. Interestingly, Yamanaka factors elevated the levels of migrating cells containing the neurogenic markers doublecortin and calretinin, and the levels of the NMDA receptor subunit GluN2B. These changes could result in an increase in the survival of newborn DG neurons during their maturation and higher synaptic plasticity in mature neurons. Importantly, these cellular changes were accompanied by an improvement in mouse performance in the object recognition test over long time. We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases.

随着年龄的增长，翻译后表观遗传修饰发生在齿状回 (DG) 的小鼠神经元中。在这里，我们报告了 H3K9 三甲基化 (H3K9me3) 的年龄依赖性减少通过循环诱导用于细胞重编程的 Yamanaka 因子来防止。有趣的是，山中因子提高了含有神经源性标志物双皮质素和钙视网膜蛋白的迁移细胞的水平，以及 NMDA 受体亚基 GluN2B 的水平。这些变化可能导致新生 DG 神经元在成熟过程中的存活率增加，以及成熟神经元中更高的突触可塑性。重要的是，随着时间的推移，这些细胞变化伴随着对象识别测试中小鼠性能的提高。我们得出结论，体内瞬时循环重编程 在中枢神经系统中可能是改善中枢神经系统衰老和神经退行性疾病的有效策略。