Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway

Abstract

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV7.4 in outer hair cells, KV7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.

Understanding normal brain aging

“…Moreover, we focus on the two sensory systems (hearing and olfaction), prone to significant age-related deterioration. The latter are well known to predict (olfaction) or promote (hearing) mental decline [12,15].…”

“…Although aging per se is not considered as a disease, it is a major risk factor for cerebrovascular (e.g., stroke) and neurodegenerative (e.g., different kinds of dementia) diseases, which are associated with high morbidity and mortality [2,3,15]. The hearing loss may also lead to social isolation, depression, and decline of cognition [12]. In fact, the comorbidity of cognitive and sensory impairment is not rare [1,12].…”

“…The hearing loss may also lead to social isolation, depression, and decline of cognition [12]. In fact, the comorbidity of cognitive and sensory impairment is not rare [1,12]. Together, the Alzheimer's (AD) and Parkinson's (PD) diseases represent the most common forms of dementia.…”

“…AD, for instance, has a higher (1.6-3:1) prevalence in women compared to men, whereas PD has a higher (3.5:1) prevalence in men compared to women [3]. Several articles of this issue specifically address the gender-specific brain aging and its impact on sensory systems [12,15], resting-state functional connectivity of brain networks [6], and quality of sleep [4].…”

“…Finally, many articles of this special issue compare aging of brain architecture and function (including sensory processing, cognitive abilities, and sleep) between humans and commonly used laboratory animals (rats and mice) [4,8,[12][13][14][15]17]. The common mechanisms identified in these studies shall enable high-resolution analyses of key cellular/ molecular pathways involved as well as the future development of therapeutics supporting the cognitive longevity or even reverting the age-induced impairment of cognition.…”