Abstract |
Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1(δ/-) mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1(δ/-) mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1(δ/-) mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.
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Authors | Marcella Spoor, A Paul Nagtegaal, Yanto Ridwan, Nils Z Borgesius, Bart van Alphen, Ingrid van der Pluijm, Jan H J Hoeijmakers, Maarten A Frens, J Gerard G Borst |
Journal | Mechanisms of ageing and development
(Mech Ageing Dev)
2012 Feb-Mar
Vol. 133
Issue 2-3
Pg. 59-67
ISSN: 1872-6216 [Electronic] Ireland |
PMID | 22257940
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Cross-Linking Reagents
- DNA-Binding Proteins
- DNA
- Endonucleases
- Ercc1 protein, mouse
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Topics |
- Aging
- Animals
- Cross-Linking Reagents
(chemistry)
- DNA
(metabolism)
- DNA Damage
- DNA Repair
- DNA-Binding Proteins
(genetics)
- Electrodes
- Endonucleases
(genetics)
- Hearing
- Hearing Loss
(genetics)
- Immunohistochemistry
(methods)
- Mice
- Mutation
- Otoacoustic Emissions, Spontaneous
(physiology)
- Saccades
(genetics)
- Vision Disorders
(genetics)
- Vision, Ocular
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