Abstract
Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.
Highlights
Age-related hearing loss (AHL), known as presbycusis, is the most common sensory disorder among elderly persons
We found that the expression of Sirt3 and SOD2 changed with age; age had less of an effect on SOD2 mRNA expression
Our results showed that compared to the NS group, the protein levels of Sirt3 in the age-matched D-Gal group were reduced by 1.46, 2.10- and 3.47-fold (P,0.01), and those of SOD2 were reduced by 1.03, 1.10- (P.0.05) and 2.27-fold (P,0.05), respectively
Summary
Age-related hearing loss (AHL), known as presbycusis, is the most common sensory disorder among elderly persons. The decline in hearing sensitivity caused by aging is related to the deterioration of the central and/or peripheral auditory system [1]. The prevailing otolaryngologic approach to the treatment of AHL emphasizes the compensation of peripheral functional deficits, such as hearing aids and cochlear implants. A better understanding of the molecular mechanisms underlying AHL may overcome this obstacle by opening doors to new treatment options, such as drug therapy in the auditory system. Age-related dysfunction of the central auditory cortex is well known to affect sound localization [3]. Because traditional surgery is not suitable for central presbycusis, illustrating the pathological process and identifying potential therapeutic targets are important
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