Sirt1 deficiency protects cochlear cells and delays the early onset of age-related hearing loss in C57BL/6 mice

Abstract Hearing gradually declines with age in both animals and humans and this condition is known as age-related hearing loss. Here, we investigated the effects of deficiency of Sirt1 , a member of the mammalian sirtuin family, on age-related cochlear pathology and associated hearing loss in C57BL...

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Bibliographic Details
Published in:Neurobiology of aging 2016-07, Vol.43, p.58-71
Main Authors: Han, Chul, Linser, Paul, Park, Hyo-Jin, Kim, Mi-Jung, White, Karessa, Vann, James M, Ding, Dalian, Prolla, Tomas A, Someya, Shinichi
Format: Article
Language:English
Subjects:
Acetylation
Aging
Aging - pathology
Aging - physiology
Animals
Catalase - metabolism
Cell Line
Cell Survival
Disease Models, Animal
Ear, Inner - cytology
Ear, Inner - metabolism
Female
Forkhead Box Protein O3 - metabolism
Gene Knockdown Techniques
Hair Cells, Auditory - pathology
Hearing loss
Hearing Loss - etiology
Hearing Loss - pathology
Hearing Loss - prevention & control
Inner ear
Internal Medicine
Male
Mice, Inbred C57BL
Neurology
Oxidative Stress
Sirtuin
Sirtuin 1 - deficiency
Sirtuin 1 - physiology
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Summary:Abstract Hearing gradually declines with age in both animals and humans and this condition is known as age-related hearing loss. Here, we investigated the effects of deficiency of Sirt1 , a member of the mammalian sirtuin family, on age-related cochlear pathology and associated hearing loss in C57BL/6 mice, a mouse model of early-onset age-related hearing loss. Sirt1 deficiency reduced age-related oxidative damage of cochlear hair cells and spiral ganglion neurons, and delayed the early onset of age-related hearing loss. In cultured mouse inner ear cell lines, Sirt1 knockdown increased cell viability under oxidative stress conditions, induced nuclear translocation of Foxo3a, and increased acetylation status of Foxo3a. This resulted in increased activity of the antioxidant enzyme catalase. In young wild-type mice, both Sirt1 and Foxo3a proteins resided in the cytoplasm of the supporting cells within the organ of Corti of the cochlea. Therefore, our findings suggest that SIRT1 promotes early-onset age-related hearing loss through suppressing FOXO3a-mediated oxidative stress resistance in the cochlea of C57BL/6 mice.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2016.03.023