Bigland Mark J, Brichta Alan M, Smith Doug W
Neurobiology of Ageing and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia.
Preclinical Neurobiology Program, Priority Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia.
Curr Aging Sci. 2018;11(2):108-117. doi: 10.2174/1874609811666180830143358.
Deterioration in vestibular function occurs with ageing and is linked to age-related falls. Sensory hair cells located in the inner ear vestibular labyrinth are critical to vestibular function. Vestibular hair cells rely predominantly on oxidative phosphorylation (OXPHOS) for energy production and contain numerous mitochondria. Mitochondrial DNA (mtDNA) mutations and perturbed energy production are associated with the ageing process.
We investigated the effects of ageing on mtDNA in vestibular hair and support cells, and vestibular organ gene expression, to better understand mechanisms of age-related vestibular deficits.
Vestibular hair and supporting cell layers were microdissected from young and old rats, and mtDNA was quantified by qPCR. Additionally, vestibular organ gene expression was analysed by microarray and gene set enrichment analyses.
In contrast to most other studies, we found no evidence of age-related mtDNA deletion mutations. However, we found an increase in abundance of major arc genes near the mtDNA control region. There was also a marked age-related reduction in mtDNA copy number in both cell types. Vestibular organ gene expression, gene set enrichment analysis showed the OXPHOS pathway was down regulated in old animals.
Given the importance of mtDNA to mitochondrial OXPHOS and hair cell function, our findings suggest the vestibular organs are potentially on the brink of an energy crisis in old animals.
前庭功能会随着年龄增长而衰退，且与年龄相关的跌倒有关。位于内耳前庭迷路的感觉毛细胞对前庭功能至关重要。前庭毛细胞主要依靠氧化磷酸化（OXPHOS）来产生能量，并且含有大量线粒体。线粒体DNA（mtDNA）突变和能量产生紊乱与衰老过程相关。
我们研究了衰老对前庭毛细胞和支持细胞中线粒体DNA以及前庭器官基因表达的影响，以更好地理解与年龄相关的前庭功能缺陷的机制。
从年轻和老年大鼠中显微解剖出前庭毛细胞层和支持细胞层，通过定量聚合酶链反应（qPCR）对线粒体DNA进行定量分析。此外，通过微阵列和基因集富集分析来分析前庭器官的基因表达。
与大多数其他研究不同，我们没有发现与年龄相关的线粒体DNA缺失突变的证据。然而，我们发现线粒体DNA控制区附近的主要弧基因丰度增加。两种细胞类型中的线粒体DNA拷贝数也都有明显的与年龄相关的减少。前庭器官基因表达、基因集富集分析表明，老年动物的氧化磷酸化途径下调。
鉴于线粒体DNA对线粒体氧化磷酸化和毛细胞功能的重要性，我们的研究结果表明，老年动物的前庭器官可能正处于能量危机的边缘。
