In search of biophyscial model for age related hearing loss ARHL for precision therapeutic studies

Abstract

Aging is an inevitable and involuntary process, associated with gradual deterioration of health. newlineAge-related hearing loss (ARHL) is one of the most frequent sensory disabilities which advances newlinewith age. ARHL is a multifactorial aging disorder and is mostly affected by environmental, newlinelifestyle, genetic factors, and fluctuation in the inner ear fluid composition with age. These factors newlineirreversibly and slowly damage the integrity of the auditory machinery present in the inner ear. newlineAuditory machinery is precisely composed of tiny hair cells along with the stereocilia which are newlineprojected vertically in a stairway manner. The deflection of these stereocilia helps in decoding newlinesound from mechanical stimuli to electrical signals. The top of the consecutive stereocilia is newlineanchored through thin filamentous proteins called tip links. These tip links are held together by newlinetwo proteins, protocadherin-15 (Pcdh15) from the bottom and cadherin-23 (Cdh23) from the top. newlineThese proteins interact in a handshake conformation and act as a gating channel for newlinemechanotransduction of sound. Out of these two proteins, the Cdh23 is mapped with the ARHL newlinephenotype, and mutations in the Cdh23 are marked with congenital as well as progressive hearing newlineloss (PHL). PHL is an accelerated state of ARHL that marks the early onset of hearing loss and newlinedrives towards complete hearing loss at a relatively faster rate compared to ARHL. The lack of newlineany biophysical models deciphering the molecular basis of senile deafness is the major bottleneck newlinein designing the precise therapeutic remedy.