title: Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.
abstract: 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 & NOTEWORTHYIn 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.
authors.affiliation: Tianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Sport Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, China.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Kou
authors.affiliation: Graduate School, Wuhan Sports University, Wuhan, China; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Graduate School, Wuhan Sports University, Wuhan, China; and.
authors.forename: Xingran
authors.initials: X
authors.lastname: Liu
authors.affiliation: Graduate School, Wuhan Sports University, Wuhan, China; and.
authors.forename: Jingru
authors.initials: J
authors.lastname: Chang
authors.affiliation: Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Tianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Sport Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Jia
authors.affiliation: Tianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Sport Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Tianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Sport Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, China; nchen510@gmail.com.
authors.forename: Ning
authors.identifier: http://orcid.org/0000-0002-8191-6744
authors.initials: N
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D034281:Dynamins / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D034281:Dynamins; D005690:Galactose
keywords: aging; autophagy; miR-34a; mitochondrial dynamics; swimming training