Aging of the nervous system, and the occurrence of age-related brain diseases such as stroke, are associated with changes to a variety of cellular processes controlled by many distinct genes. MicroRNAs (miRNAs), short non-coding functional RNAs that can induce translational repression or site-specific cleavage of numerous target mRNAs, have recently emerged as important regulators of cellular senescence, aging, and the response to neurological insult. Here, we focused on the assessment of the role of miR-34a in stroke. We noted increases in miR-34a expression in the blood of stroke patients as well as in blood and brain of mice subjected to experimental stroke. Our methodical genetic manipulation of miR-34a expression substantially impacted stroke-associated preclinical outcomes and we have in vitro evidence that these changes may be driven at least in part by disruptions to blood brain barrier integrity and mitochondrial oxidative phosphorylation in endothelial cells. Finally, aging, independent of brain injury, appears to be associated with shifts in circulating miRNA profiles. Taken together, these data support a role for miRNAs, and specifically miR-34a, in brain aging and the physiological response to age-related neurological insult, and lay the groundwork for future investigation of this novel therapeutic target.

中文翻译：

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MiR-34a和中风：脑缺血中不可改变的生物学危险因素的评估。

神经系统的衰老以及与年龄相关的脑部疾病（如中风）的发生与许多受不同基因控制的细胞过程的变化有关。MicroRNA（miRNA）是一种短的非编码功能性RNA，可以诱导许多目标mRNA的翻译抑制或位点特异性切割，最近已成为细胞衰老，衰老和对神经损伤反应的重要调节剂。在这里，我们集中于评估miR-34a在中风中的作用。我们注意到中风患者血液以及实验性中风小鼠的血液和大脑中miR-34a表达的增加。我们对miR-34a表达进行的有条不紊的遗传操作显着影响了与中风相关的临床前结果，并且我们有体外证据表明，这些变化可能至少部分受到内皮细胞中血脑屏障完整性和线粒体氧化磷酸化的破坏的驱动。最后，衰老与大脑损伤无关，似乎与循环miRNA谱的改变有关。综上所述，这些数据支持miRNA，尤其是miR-34a在脑衰老以及对与年龄相关的神经损伤的生理反应中的作用，并为该新治疗靶标的未来研究奠定了基础。似乎与循环miRNA谱的变化有关。综上所述，这些数据支持miRNA，尤其是miR-34a在脑衰老以及对与年龄相关的神经损伤的生理反应中的作用，并为该新治疗靶标的未来研究奠定了基础。似乎与循环miRNA谱的变化有关。综上所述，这些数据支持miRNA，尤其是miR-34a在脑衰老以及对与年龄相关的神经损伤的生理反应中的作用，并为该新治疗靶标的未来研究奠定了基础。