title: Anatomical, metabolic and genetic aspects of age-related hearing loss in mice.
abstract: Because of their short lifespan and genetic homogeneity, mice can provide valuable insights into the biological basis of age-related hearing loss. In C57BL/6 mice, hair cell loss begins around 1-2 months of age and progresses rapidly along a base-to-apex gradient, whereas CBA mice show relatively little hair cell loss until late in life. This anatomical difference is reflected in dehydrogenase histochemistry, an indirect measure of aerobic energy metabolism. A small, but significant, decrease in hair cell dehydrogenase staining occurred in CBA mice between 1.5 and 18 months of age. Significantly, dehydrogenase levels in 1.5-month C57 mice were substantially lower than in CBA mice of any age. Thus, deficits in aerobic energy metabolism presage degeneration of the hair cells. The superoxide radical, O2*-, a normal byproduct of cellular metabolism, is potentially toxic and can cause cellular damage if it is not inactivated by superoxide dismutases. Cytosolic copper/zinc superoxide dismutase (SOD1) is highly expressed in the cochlea. Knockout mutant mice with a single (HET) or double deletion (KO) of the Sod1 gene coding for SOD1 showed greater age-related losses than wild-type (WT) mice. KO mice had the worst hearing, WT the best, and HETs were intermediate. KOs exhibited considerably greater hair cell loss than WT mice; however, losses in KOs were only slightly greater than in HETs. KO mice showed significantly greater loss of spiral ganglion cells and nerve fibers than WT mice. These results indicate that SOD1 and O2*- play important roles in age-related hearing loss. Intervention strategies targeting O2*- may reduce age-related hearing loss.
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: McFadden
authors.forename: D
authors.initials: D
authors.lastname: Ding
authors.forename: R
authors.initials: R
authors.lastname: Salvi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003638:Deafness / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005838:Genotype; D006199:Hair Cells, Auditory, Inner / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009925:Organ of Corti / Q000473:pathology*; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics
chemical_list: D013482:Superoxide Dismutase