Age-related Hearing Loss in C57BL/6J Mice is Mediated by Bak-dependent Mitochondrial Apoptosis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Nov 11

PMID 19901338

Citations 173

Authors

Shinichi Someya

Jinze Xu

Kenji Kondo

Dalian Ding

Richard J Salvi

Tatsuya Yamasoba

Peter S Rabinovitch

Richard Weindruch

Christiaan Leeuwenburgh

Masaru Tanokura

Tomas A Prolla

Affiliations

Soon will be listed here.

Abstract

Age-related hearing loss (AHL), known as presbycusis, is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. The molecular mechanisms underlying AHL are unknown, and currently there is no treatment for the disorder. Here we report that C57BL/6J mice with a deletion of the mitochondrial pro-apoptotic gene Bak exhibit reduced age-related apoptotic cell death of spiral ganglion neurons and hair cells in the cochlea, and prevention of AHL. Oxidative stress induces Bak expression in primary cochlear cells, and Bak deficiency prevents apoptotic cell death. Furthermore, a mitochondrially targeted catalase transgene suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Oral supplementation with the mitochondrial antioxidants alpha-lipoic acid and coenzyme Q(10) also suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Thus, induction of a Bak-dependent mitochondrial apoptosis program in response to oxidative stress is a key mechanism of AHL in C57BL/6J mice.

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