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. 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.

Exercise Attenuates Brain Aging by Rescuing Down-Regulated Wnt/β-Catenin Signaling in Aged Rats

“…Therefore, DKK1 plays a key role in influencing cognitive function through Wnt signaling. In addition, Sirt1 plays critical roles in a series of brain functions; as confirmed by one of previous studies with the significant down-regulation of Sirt1 in oxidative stress-induced AD rats and obvious up-regulation of Sirt1 upon 8-week swimming intervention, thereby improving cognitive function (Kou et al, 2017). Due to the cross-talk among DKK-1, Sirt1 and p53, we have also determined the relationships among DKK-1, Sirt1 and p53 in hippocampal tissues of aged rats.…”

Excessive Treadmill Training Enhances Brain-Specific MicroRNA-34a in the Mouse Hippocampus

“…its suppression may be generally neuroprotective (Horst et al, 2017). Moreover, swimming intervention can delay d-galactoseinduced brain aging in rats via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics (Kou et al, 2017). However, an increase in miR-34a level in the OT group was observed in the present study, indicating that excessive training may activate these maladaptation consequences.…”

The Regulation of microRNAs in Alzheimer's Disease

“…Our research team has also found that swimming intervention with a period of 8 weeks can attenuate brain aging in D-galactose-induced AD rats. Mechanically, swimming training down-regulates miR-34a expression in AD rats, which is also confirmed by miR-34a inhibitor in SH-SY5Y cells (78). In normally aged mice, resveratrol treatment can improve learning and memory capacity through down-regulating miR-124/-134, in turn, activating CREB-BDNF signal pathway, which suggests that a resveratrolrich diet may be beneficial for preserving cognitive function in aged individuals (79).…”