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Mitochondrial DNA deletions associated with aging and presbyacusis
1Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, West Bloomfield, MI 48323, USA.
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.
Design:
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.
Subjects:
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.
Insights
Aging is linked to hearing loss (presbyacusis) through mitochondrial DNA damage. A specific 4834-base pair deletion in mitochondrial DNA increases with age, potentially causing cellular dysfunction and hearing impairment.
Area of Science:
- Gerontology
- Molecular Biology
- Auditory Neuroscience
Background:
- The membrane hypothesis of aging links aging processes to reactive oxygen metabolites and mitochondrial DNA damage.
- Accumulated mitochondrial DNA damage leads to cellular bioenergetic deficiency, dysfunction, and organ failure, forming the basis of this hypothesis.
- Reactive oxygen metabolites, by-products of cellular respiration, can damage mitochondrial DNA, contributing to aging.
Purpose of the Study:
- To investigate the potential role of the membrane hypothesis of aging in the development of presbyacusis (age-related hearing loss).
Main Methods:
- Auditory sensitivity was assessed in Fischer rats across four age groups using auditory brainstem response.
- Mitochondrial DNA was analyzed from brain, stria vascularis, and auditory nerve tissues.
- Specific gene segments and a 4834-base pair deletion associated with aging were amplified and identified.
Main Results:
- Auditory sensitivity progressively decreased with increasing age in the rats.
- A significant increase in the 4834-base pair mitochondrial DNA deletion was observed in older rats compared to younger ones.
Conclusions:
- The 4834-base pair mitochondrial DNA deletion is significantly associated with aging in Fischer rats.
- These findings suggest a potential link between this mitochondrial DNA deletion and the development of presbyacusis.