In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance

This study is the first to exclusively partially reprogram a specific subpopulation of neurons in the cerebral cortex of aged mice. The in vivo model demonstrated that YF expression in postmitotic neurons does not dedifferentiate them, and it avoids deleterious effects observed with YF expression in other cell types. Additionally, our study has demonstrated that only cyclic, not continuous, expression of YF resulted in a noteworthy enhancement of cognitive function in adult mice.

本研究为首例专门针对衰老小鼠大脑皮层内特定神经元亚群开展局部重编程的研究。该体内模型证实，在有丝分裂后神经元中表达YF不会使其发生去分化，同时规避了在其他细胞类型中表达YF时所观察到的有害效应。此外，本研究还证实，仅YF的周期性（而非持续性）表达可使成年小鼠的认知功能得到显著提升。