Chronic inflammation – inflammaging – in the ageing cochlea: A novel target for future presbycusis therapy

Abstract

Chronic, low-grade inflammation, or inflammaging, is a crucial contributor to various age-related pathologies and natural processes in aging tissue, including the nervous system. Over the past two decades, much effort has been done to understand the mechanisms of inflammaging in disease models such as type II diabetes, cardiovascular disease, Alzheimer’s disease, Parkinson’s disease, and others. However, despite being the most prevalent neurodegenerative disorder, the number one communication disorder, and one of the top three chronic medical conditions of our aged population; little research has been conducted on the potential role of inflammation in age-related hearing loss (ARHL). Recently, it has been suggested that there is an inflammatory presence in the cochlea, perhaps involving diffusion processes of the blood-brain barrier as it relates to the inner ear. Recent research has found correlations between hearing loss and markers such as C-reactive protein, IL-6, and TNF-α indicating inflammatory status in human case-cohort studies. However, there have been very few reports of in vivo research investigating the role of chronic inflammation’s in hearing loss in the aging cochlea. Future research directed at better understanding the mechanisms of inflammation in the cochlea as well as the natural changes acquired with aging may provide a better understanding of how this process can accelerate presbycusis. Animal model experimentation and pre-clinical studies designed to recognize and characterize cochlear inflammatory mechanisms may suggest novel treatment strategies for preventing or treating ARHL. In this review, we seek to summarize key research in chronic inflammation, discuss its implications for possible roles in ARHL, and finally suggest directions for future investigations.

Augmentation of cellular NAD+ by NQO1 enzymatic action improves age‐related hearing impairment

“…Aging is characterized by increased oxidative stress and inflammation, and has been reported to have a relationship with ARHL and chronic inflammatory diseases, such as diabetes and cardiovascular disease (Watson et al, ). Additionally, previous studies have demonstrated that increased ROS production and pro‐inflammatory cytokines, such as TNF‐α, IL‐1β, and IL‐6, play critical roles in cochlear tissue damage, in noise‐ or cisplatin‐induced hearing loss (Fujioka et al, ; So et al, ).…”

“…NF‐κB transcription factor is considered as the master regulator of the inflammatory response, which is associated with the development and pathogenesis of various age‐related diseases, including ARHL (Kubben & Misteli, ; Watson et al, ). According to a recent report, daily fasting (a type of dietary restriction) protects the rat heart against age‐induced inflammation and fibrosis, by suppressing NF‐κB activation and oxidative damage, indicating the preventive effect of NF‐κB inhibition, on age‐related diseases (Castello et al, ).…”

“…Although the use of hearing aids or cochlear implants improves related symptoms considerably, ARHL still remains largely untreated (Choi et al, ). Despite the fact that the mechanism of ARHL has remained elusive, multiple studies have demonstrated that age‐dependent alterative oxidative stress, reactive oxygen species (ROS) metabolism, up‐regulation of inflammatory responses, and mitochondrial dysfunction in parallel with cellular signaling and gene expression are implicated in this process (Fujimoto & Yamasoba, ; Watson, Ding, Zhu, & Frisina, ). Particularly, structural changes and degeneration of inner ear cells, such as sensory hair cells, spiral ganglion neurons, and stria vascularis, are characteristics of aged mammals (Revuelta et al, ).…”

The Changing Landscape of Naive T Cell Receptor Repertoire With Human Aging

“…It also dampens the effect of vaccination ( 6 – 8 ) and can lead to higher cancer susceptibility ( 9 – 12 ). These changes may further result in an imbalanced immune response that can develop into non-specific inflammation, provoking neurodegenerative and cardiovascular disorders, and to the loss of tolerance, leading to autoimmunity ( 3 , 13 – 15 ). For the latter, a reduction of regulatory T cell (Treg) diversity ( 16 , 17 ) could be a one of the causative factors.…”

Association of inflammatory markers with hearing impairment: The English Longitudinal Study of Ageing

“…Our study supports both these mechanisms, given that inflammation and several CVD risk factors such as smoking, physical inactivity and obesity were predictive of an increased risk of hearing impairment. Inflammageing-related diseases such as obesity, hypertension and type 2 diabetes have been linked to poorer hearing in previous studies 43 . Moreover, our results and a large body of studies, including animal models, make a direct inflammatory role plausible in the aetiology of age-related hearing loss.…”