Swimming attenuates D-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics
Swimming attenuates D-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics
复制标题
游泳通过抑制 miR-34a 介导的自噬损伤和异常线粒体动力学来减轻 d-半乳糖诱导的大脑衰老。
DOI：
10.1152/japplphysiol.00018.2017
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发表时间：
2017-06-01
影响因子：
3.3
通讯作者：
Chen, Ning
中科院分区：
文献类型：
--
作者：
Kou, Xianjuan;Li, Jie;Chen, Ning
microRNAs（miRNAs）参与了多种神经退行性疾病的发生发展。为了探讨运动干预过程中miR-34 a在阿尔茨海默病（AD）等衰老相关疾病中的调节作用，我们构建了d-半乳糖（d-gal）诱导的氧化应激和认知障碍伴自噬功能障碍和线粒体动力学异常的大鼠模型，测定了游泳干预对d-gal诱导的衰老大鼠认知障碍的缓解作用，并评估了miR-34 a介导的自噬功能状态和异常线粒体动力学。与此同时，通过转染miR-34 a抑制剂，在miR-34 a沉默的人SH-SY 5 Y细胞中证实了miR-34 a的上调是否会导致自噬功能失调和线粒体动力学异常。结果表明，游泳干预可显著改善d-gal衰老模型大鼠的认知功能障碍，阻止miR-34 a的上调，减轻自噬功能障碍，抑制dynamin-related protein 1（DRP 1）的增加。相反，在细胞模型中，miR-34 a抑制剂不仅减弱了D-gal诱导的自噬损伤，而且降低了DRP 1和线粒体融合蛋白2（MFN 2）的表达。因此，游泳训练可以通过减轻miR-34 a介导的自噬损伤和线粒体动力学异常来延缓d-gal诱导的衰老大鼠的脑衰老，miR-34 a可能是衰老相关疾病如AD的新的治疗靶点。NEW & NOTEWORTHY在本研究中，我们发现miR-34 a的上调是衰老或衰老相关疾病的标志，其可导致功能失调的自噬和异常的线粒体动力学。相比之下，游泳干预可以通过抑制miR-34 a挽救受损的自噬功能状态和异常的线粒体动力学来延缓衰老过程。
microRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. To explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with d-galactose (d-gal)-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of d-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the upregulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of a miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, prevent the upregulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of dynamin-related protein 1 (DRP1) in d-gal-induced aging model rats. In contrast, the miR-34a inhibitor in cell model not only attenuated D-gal-induced the impairment of autophagy but also decreased the expression of DRP1 and mitofusin 2 (MFN2). Therefore, swimming training can delay brain aging of d-gal-induced aging rats through attenuating the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD.NEW & NOTEWORTHY In the present study, we have found that the upregulation of miR-34a is the hallmark of aging or aging-related diseases, which can result in dysfunctional autophagy and abnormal mitochondrial dynamics. In contrast, swimming intervention can delay the aging process by rescuing the impaired functional status of autophagy and abnormal mitochondrial dynamics via the suppression of miR-34a.