Mitochondrial DNA deletions associated with aging and presbyacusis
- PMID: 9339978
- DOI: 10.1001/archotol.1997.01900100009001
Mitochondrial DNA deletions associated with aging and presbyacusis
Abstract
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.
Similar articles
-
Biologic activity of mitochondrial metabolites on aging and age-related hearing loss.Am J Otol. 2000 Mar;21(2):161-7. doi: 10.1016/s0196-0709(00)80003-4. Am J Otol. 2000. PMID: 10733178
-
Effects of dietary restriction and antioxidants on presbyacusis.Laryngoscope. 2000 May;110(5 Pt 1):727-38. doi: 10.1097/00005537-200005000-00003. Laryngoscope. 2000. PMID: 10807352 Review.
-
Influence of lecithin on mitochondrial DNA and age-related hearing loss.Otolaryngol Head Neck Surg. 2002 Sep;127(3):138-44. doi: 10.1067/mhn.2002.127627. Otolaryngol Head Neck Surg. 2002. PMID: 12297801
-
[Mitochondrial DNA large deletions associated with presbycusis].Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2003 Nov;17(11):678-80. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2003. PMID: 14971208 Chinese.
-
Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage.Acta Otolaryngol Suppl. 2004 May;(552):16-24. doi: 10.1080/03655230410017823. Acta Otolaryngol Suppl. 2004. PMID: 15219042 Review.
Cited by
-
Role of Oxidative Stress in Sensorineural Hearing Loss.Int J Mol Sci. 2024 Apr 9;25(8):4146. doi: 10.3390/ijms25084146. Int J Mol Sci. 2024. PMID: 38673731 Free PMC article. Review.
-
Age-related changes in antioxidant enzymes related to hydrogen peroxide metabolism in rat inner ear.Neurosci Lett. 2009 Oct 16;464(1):22-5. doi: 10.1016/j.neulet.2009.08.015. Epub 2009 Aug 11. Neurosci Lett. 2009. PMID: 19679169 Free PMC article.
-
Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss.Mol Brain. 2021 May 17;14(1):82. doi: 10.1186/s13041-021-00791-w. Mol Brain. 2021. PMID: 34001214 Free PMC article.
-
Age-related hearing loss or presbycusis.Eur Arch Otorhinolaryngol. 2010 Aug;267(8):1179-91. doi: 10.1007/s00405-010-1270-7. Epub 2010 May 13. Eur Arch Otorhinolaryngol. 2010. PMID: 20464410 Review.
-
Pathology and mechanisms of cochlear aging.J Neurosci Res. 2020 Sep;98(9):1674-1684. doi: 10.1002/jnr.24439. Epub 2019 May 7. J Neurosci Res. 2020. PMID: 31066107 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical