Autophagy is Protective in the Progression Towards Age-Related Hearing Loss
This open access paper provides a good summary of present thought on the contributing causes of hearing loss, in which the various issues of noise, aging, and toxicity cause harm via inducing stress in hair cells of the inner ear and their axonal connections to the brain. Autophagy is a cell maintenance process, the recycling of damaged component parts. More efficient autophagy helps hair cells to resist and survive a stressful environments, but autophagy declines with age. Defects arise in many of the component parts of the autophagic system and its regulation. This is likely why the threshold for loss of hair cells in response to stresses diminishes in later life, leading to the onset of hearing loss in a large fraction of the population.
Hearing loss is not only a physical and financial burden in social life, but also causes psychological problems and psychiatric disorders, including cognitive decline and depression. Genetic alterations, noise, ototoxic drugs, and aging can all contribute to hearing loss. Although the causes vary, the most common causes of deafness are damage or loss of hair cells (HCs) and degeneration of spiral ganglion neurons (SGNs). HCs are responsible for converting external sound signals into electrical signals that are transmitted to the brainstem through SGNs. Recent studies have shown that these sensory cells cannot spontaneously regenerate in adult mammals, so damage or loss of HCs and degeneration of SGNs can result in permanent deafness.
Autophagy is responsible for normal cell survival and homeostasis. A variety of human conditions, such as neurodegenerative diseases, cancer, and inflammation, have been reported to be associated with dysregulated autophagic processes. In the inner ear, many studies have shown that autophagy played an important role in cell development, differentiation, and survival, and recently there has been renewed interest in regulating autophagy to prevent sensorineural hearing loss (SNHL).
Noise and ototoxic drugs increased the levels of oxidative stress in HCs, which contributed to cell death, and in a mouse model that was exposed to noise, the level of autophagy was increased in HCs. It is worth noting that the oxidative stress level in response to noise was dose dependent, and moderate noise induced temporary threshold shifts and increased the level of autophagy in outer hair cells, while severe noise produced excess reactive oxygen species (ROS) that induced permanent threshold shifts. Increasing autophagy with rapamycin can reduce the accumulation of ROS and prevent cell death from noise exposure. In contrast, blocking autophagy via pharmacological or genetic means can increase the accumulation of ROS and promote cell death.
Presbycusis (age-related hearing loss) is a common sensory disorder associated with aging. The level of autophagy decreases with age, and the upregulation of autophagy can promote aging HC survival and slow the degeneration of auditory cells. Though we have known that some proteins and miRNAs participate in the autophagic pathways involved in SNHL making them potential targets for treatment of SNHL, the specific signaling pathways they participate in remain unclear, let alone the known connections between these proteins and miRNAs. The application of autophagy as a treatment for deafness is still a long way off. Current research has been limited to cell lines, explants, and animals, and few clinical trials have examined the role of autophagy. Given the complexity of mechanisms and functions of autophagy, the safest and most effective strategies must be studied in future research.