Mitochondrial DNA deletions associated with aging and presbyacusis.
BACKGROUND
The membrane hypothesis of aging proposes an association between reactive oxygen metabolites and aging processes. Reactive oxygen 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 activities of reactive oxygen metabolites, also known as free oxygen radicals, is direct damage to mitochondrial DNA. Progressive accumulation of mitochondrial DNA damage renders cells unable to conduct oxidative phosphorylation reactions effectively, thereby leading to a bioenergetically 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 hypothesis of aging may be involved in the development of presbyacusis.


METHODS
Fischer rats from 4 age groups were tested for auditory sensitivity using the auditory brainstem response. Brain, stria vascularis, and auditory nerve tissues were harvested and mitochondrial DNA was amplified 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) deletion associated with aging.


METHODS
Fischer rats (n=28) from 4 age groups 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 sensitivity with age. The mitochondrial DNA studies identify a significant increase in the presence of the 4834-bp deletion in the aged subjects compared with the young.


CONCLUSIONS
These findings raise the possibility that the 4834-bp deletion may be associated with presbyacusis, as well as with aging.
Seidman
M D
MD
Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, West Bloomfield, MI 48323, USA.
Bai
U
U
Khan
M J
MJ
Quirk
W S
WS
D000375:Aging / Q000235:genetics*; D000818:Animals; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005072:Evoked Potentials, Auditory; D017353:Gene Deletion; D008297:Male; D011304:Presbycusis / Q000235:genetics* / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344
D017931:DNA Primers; D004272:DNA, Mitochondrial