Neurobiology of age related hearing loss

Description

The deterioration of hearing function, particularly at high frequencies, is a process that inevitably accompanies aging in humans as well as in other mammals. The etiology of the disease remains unknown, although, as in other age related diseases, histopathological abnormalities can be identified. The knowledge of the neurobiological mechanisms may be useful to understand the pathophysiology of presbycusis and thus define new therapeutic strategies.Somatic mitochondrial DNA (mtDNA) deletions have been associated with the process of aging in many postmitotic tissues. The cochlear tissues are known to contain an abundance of mitochondria, and this observation has prompted a search for mtDNA deletions in the cochlea. The presence of the common deletion (CD) has been reported in the mtDNA isolated from cochlear tissues of individuals with presbycusis. The function of the cochlea is to convert an acoustic signal into an electrochemical stimulus, which is then transmitted to the central nervous system. Cochlea tissue like muscle, heart, and brain tissues has an abundance of mitochondria and is expected to be heavily dependent on functional mitochondria. The role of mtDNA mutations in presbycusis and aging has been investigated: an high frequency of mtDNA point mutations has been reported in temporal bones of individuals with presbycusis. The consequence of mtDNA mutations is a deficit in energy metabolism and their presence may trigger apoptosis; mtDNA mutations only become physiologically important when a threshold level is exceeded. This level may vary between tissues based on the energy metabolism required for function.Mitochondrial dysfunction plays a role in the pathogenesis of presbycusis, and bioenergetics agents such as creatine, coenzyme Q10, or nicotinamide may be neuroprotective in presbycusis.Coenzyme Q10 inhibits lipid peroxidation by either scavenging free radicals directly or by reducing a-tocopheroxyl radical to a-tocopherol. Coenzyme Q10 protects membrane proteins against oxidation. Coenzyme Q10 also inhibits DNA oxidation in rat liver mitochondria and inhibits DNA strand breaks in human lymphocytes. In the cochlea, coenzyme Q10 presumably prevents lipid oxidation, protein oxidation, and DNA damage.The findings illustrated in this chapter represent the experimental basis for the development of a new therapies in the treatment of presbycusis, addressed to prevent lipid peroxidation and mitochondrial damage.

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