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首页> 外文期刊>Aging cell. >Increased gene dosage of Ink4/Arf and p53 delays age-associated central nervous system functional decline
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Increased gene dosage of Ink4/Arf and p53 delays age-associated central nervous system functional decline

机译：Ink4 / Arf和p53基因剂量的增加延迟了与年龄相关的中枢神经系统功能下降

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The impairment of the activity of the brain is a major feature of aging, which coincides with a decrease in the function of neural stem cells. We have previously shown that an extra copy of regulated Ink4/Arf and p53 activity, in s-Ink4/Arf/p53 mice, elongates lifespan and delays aging. In this work, we examined the physiology of the s-Ink4/Arf/p53 brain with aging, focusing on the neural stem cell (NSC) population. We show that cells derived from old s-Ink4/Arf/p53 mice display enhanced neurosphere formation and self-renewal activity compared with wt controls. This correlates with augmented expression of Sox2, Sox9, Glast, Ascl1, and Ars2 NSC markers in the subventricular zone (SVZ) and in the subgranular zone of the dentate gyrus (DG) niches. Furthermore, aged s-Ink4/Arf/p53 mice express higher levels of Doublecortin and PSA-NCAM (neuroblasts) and NeuN (neurons) in the olfactory bulbs (OB) and DG, indicating increased neurogenesis invivo. Finally, aged s-Ink4/Arf/p53 mice present enhanced behavioral and neuromuscular coordination activity. Together, these findings demonstrate that increased but regulated Ink4/Arf and p53 activity ameliorates age-related deterioration of the central nervous system activity required to maintain the stem cell pool, providing a mechanism not only for the extended lifespan but also for the health span of these mice.
机译：大脑活动的损害是衰老的主要特征，这与神经干细胞功能的下降相吻合。先前我们已经证明，在s-Ink4 / Arf / p53小鼠中，受调节的Ink4 / Arf和p53活性的额外拷贝延长了寿命并延缓了衰老。在这项工作中，我们检查了s-Ink4 / Arf / p53大脑随年龄增长的生理，重点是神经干细胞（NSC）群体。我们显示，与wt控件相比，源自旧s-Ink4 / Arf / p53小鼠的细胞显示增强的神经球形成和自我更新活性。这与Sox2，Sox9，Glast，Ascl1和Ars2 NSC标记在脑室下区（SVZ）和齿状回（DG）壁下区的表达增强有关。此外，衰老的s-Ink4 / Arf / p53小鼠在嗅球（OB）和DG中表达较高水平的Doublecortin和PSA-NCAM（神经母细胞）和NeuN（神经元），表明体内神经发生增加。最后，老年s-Ink4 / Arf / p53小鼠表现出增强的行为和神经肌肉协调活性。总之，这些发现表明，增加但受调节的Ink4 / Arf和p53活性改善了维持干细胞池所需的与年龄相关的中枢神经系统活性下降，不仅为延长寿命提供了一种机制，而且为这些老鼠。

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