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Mitochondrial Dysfunction in Age-Related Hearing Loss

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Posted 24 March 2023 - 10:22 AM

Loss of sensory hair cells in the inner ear, or loss of the connections between these cells and the brain, drive age-related hearing loss. Researchers here focus on the contribution of mitochondrial dysfunction to this condition, alongside the decline of autophagy in older individuals, leading to poor quality control of mitochondria and consequent loss of function. Many pharmacological approaches exist or are under development to improve autophagy to a degree similar to that resulting from structured exercise programs, but compelling evidence for significantly greater improvements are so far lacking. We can reasonably debate whether or not mTOR inhibitors will represent a meaningful step beyond exercise in humans, when it comes to improved autophagy, but even there the size of the effect is not that much greater in the best case.

Hearing loss is mainly considered a sensory disorder in humans. Multiple factors contribute to the pathogenesis of sensorineural hearing loss (SNHL), such as noise exposure, ototoxic drugs, genetic mutations, aging, and chronic conditions. Histopathological changes of SNHL are characterized by mechanosensory hair cell damage, spiral ganglion neuron (SGN) loss, and stria vascularis atrophy. Emerging studies have suggested that mitochondrial DNA damage, reactive oxygen species (ROS) overproduction, and inflammatory mediators activation are associated with subsequent cochlear damage.

Mitochondria ROS could induce inflammasome activation that promotes various disease progression. Moreover, ROS could also induce cellular defense process such as autophagy, a cytoprotective mechanism that delivers damaged organelles to lysosomes for degradation. Current studies reveal autophagy exhibits an antioxidative capacity to protect against hair cell damage and possesses the potential to alleviate noise-induced hearing loss (NIHL). Autophagy not only clears up undesired proteins and damaged mitochondria (mitophagy), but also eliminate excessive ROS. Appropriate enhancement of autophagy can reduce oxidative stress, inhibit cell apoptosis, and protect auditory cells.

Link: https://doi.org/10.3...ll.2023.1119773

View the full article at FightAging

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