Genes encoding mitochondrial respiratory chain components are profoundly down-regulated with aging in the cochlea of DBA/2J mice

Abstract

Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. Mutations in the Cdh23 gene of DBA/2J mice result in AHL by 3 months of age. Hearing function was analyzed by auditory brainstem response (ABR) which confirmed that severe age-related hearing loss occurred in 8-month-old mice, whereas mild hearing loss occurred in 2-month-old mice. Cochlear gene expression of 2-month-old and 8-month-old DBA/2J mice was measured using Affymetrix microarrays. Comprehensive gene expression analysis identified significant expression changes correlated with AHL in over 4000 cochlear genes. AHL-correlated genes in the cochlea of 8-month-old DBA/2J mice were statistically associated with 15 mitochondrial process categories, including "mitochondrial electron transport chain", "oxidative phosphorylation", "respiratory chain complex I", "respiratory chain complex IV", and "respiratory chain complex V". Furthermore, 31 genes encoding components of the mitochondrial respiratory chain complexes I, II, III, IV, and V were significantly down-regulated in the cochlea. Quantitative RT-PCR (QRT-PCR) validated the microarray data in a selected set of genes. Thus, these observations provide evidence that AHL is associated with profound down-regulation of genes involved in the mitochondrial respiratory chain complexes in the cochlea of aged DBA/2J mice.