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Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis.

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.

SUBMITTER: Someya S

PROVIDER: S-EPMC2780799 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis.

Someya Shinichi S Xu Jinze J Kondo Kenji K Ding Dalian D Salvi Richard J RJ Yamasoba Tatsuya T Rabinovitch Peter S PS Weindruch Richard R Leeuwenburgh Christiaan C Tanokura Masaru M Prolla Tomas A TA

Proceedings of the National Academy of Sciences of the United States of America 20091109 46

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. Oxidat ...[more]

PMID: 19901338

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Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis.

Publications

Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis.

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