MITOCHONDRIAL-DNA DELETIONS ASSOCIATED WITH AGING AND PRESBYACUSIS

Background: The membrane hypothesis of aging proposes an association b etween reactive oxygen metabolites and aging processes. Reactive oxyge n metabolites are a normal by-product of oxidative phosphorylation and are also formed under conditions of ischemia, hypoperfusion, and as a result of environmental contaminants. Among the many detrimental acti vities of reactive oxygen metabolites, also known as free oxygen radic als, is direct damage to mitochondrial DNA. Progressive accumulation o f mitochondrial DNA damage renders cells unable to conduct oxidative p hosphorylation reactions effectively, thereby leading to a bioenergeti cally deficient cell. Over time, mitochondrial DNA damage accumulates and leads to cellular dysfunction with subsequent organ failure, aging , and ultimately, death. This sequence forms the basis of the membrane hypothesis of aging. Objective: To determine if the membrane hypothes is of aging may be involved in the development of presbyacusis. Design : Fischer rats from 4 age groups were tested for auditory sensitivity using the auditory brainstem response. Brain, stria vascularis, and au ditory nerve tissues were harvested and mitochondrial DNA was amplifie d to identify the highly conserved cytochrome b and ND1-16S ribosomal RNA segment of the NADH genes, as well as a 4834-base pair (bp) deleti on associated with aging. Subjects: Fischer rats (n=28) from 4 age gro ups were used: young (2-4 months [n=9]), mid-young (9-11 months [n=5]) , mid-old (18-20 months [n=5]), and old (30-34 months [n=9]). Results: The results demonstrate a progressive reduction in auditory sensitivi ty with age. The mitochondrial DNA studies identify a significant incr ease in the presence of the 4834-bp deletion in the aged subjects comp ared with the young. Conclusions: These findings raise the possibility that the 4834-bp deletion may be associated with presbyacusis, as wel l as with aging.