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Sirt1 deficiency protects cochlear cells and delays the early onset of age-related hearing loss in C57BL/6 mice.
Han, Chul; Linser, Paul; Park, Hyo-Jin; Kim, Mi-Jung; White, Karessa; Vann, James M; Ding, Dalian; Prolla, Tomas A; Someya, Shinichi.
Afiliação
  • Han C; Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
  • Linser P; Whitney Laboratory, University of Florida, St Augustine, FL, USA.
  • Park HJ; Department of Neurology, University of Florida, Gainesville, FL, USA.
  • Kim MJ; Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
  • White K; Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
  • Vann JM; Department of Genetics, University of Wisconsin, Madison, WI, USA; Department of Medical Genetics, University of Wisconsin, Madison, WI, USA.
  • Ding D; Center for Hearing and Deafness, State University of New York at Buffalo, NY, USA.
  • Prolla TA; Department of Genetics, University of Wisconsin, Madison, WI, USA; Department of Medical Genetics, University of Wisconsin, Madison, WI, USA.
  • Someya S; Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA. Electronic address: someya@ufl.edu.
Neurobiol Aging ; 43: 58-71, 2016 07.
Article em En | MEDLINE | ID: mdl-27255815
Hearing gradually declines with age in both animals and humans, and this condition is known as age-related hearing loss (AHL). 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 AHL. Sirt1 deficiency reduced age-related oxidative damage of cochlear hair cells and spiral ganglion neurons and delayed the early onset of AHL. 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 AHL through suppressing FOXO3a-mediated oxidative stress resistance in the cochlea of C57BL/6 mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Sirtuína 1 / Células Ciliadas Auditivas / Perda Auditiva Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neurobiol Aging Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Sirtuína 1 / Células Ciliadas Auditivas / Perda Auditiva Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neurobiol Aging Ano de publicação: 2016 Tipo de documento: Article