ArticleNeurobiology of aging2008
The role of mtDNA mutations in the pathogenesis of age-related hearing loss in mice carrying a mutator DNA polymerase gamma.
Article in Neurobiology of aging, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Expression of Wnt receptors in adult spiral ganglion neurons: frizzled 9 localization at growth cones of regenerating neurites.Neuroscience · 2009Pooled it
- Age-related hearing loss involves mitochondrial DNA instability and copy number depletion in the cochlea: Insights from in vivo and in vitro models.Hearing research · 2026Article
- Oxidative stress and reactive oxygen species in otorhinolaryngological diseases: insights from pathophysiology to targeted antioxidant therapies.Redox report : communications in free radical research · 2025Review
- Review
- Advances in the Study of Etiology and Molecular Mechanisms of Sensorineural Hearing Loss.Cell biochemistry and biophysics · 2024Review
- Hearing Loss and Oxidative Stress: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- Nanopore sequencing identifies a higher frequency and expanded spectrum of mitochondrial DNA deletion mutations in human aging.Aging cell · 2023Article
- LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss.European journal of human genetics : EJHG · 2023Article
- Taurine, Coenzyme QHearing research · 2023Review
- Redox Imbalance as a Common Pathogenic Factor Linking Hearing Loss and Cognitive Decline.Antioxidants (Basel, Switzerland) · 2023Review
- Pathogenesis and treatment progress in age-related hearing loss: a literature review.International journal of clinical and experimental pathology · 2023Review
- The roles of NADPH and isocitrate dehydrogenase in cochlear mitochondrial antioxidant defense and aging.Hearing research · 2023Review
- Mitochondrial DNA deletion mutations increase exponentially with age in human skeletal muscle.Aging clinical and experimental research · 2021Article
- Expression of G9a in Auditory Cortex Is Downregulated in a Rat Model of Age-Related Hearing Loss.Journal of molecular neuroscience : MN · 2021Article
- Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss.NPJ aging and mechanisms of disease · 2020Article
- Altered Outer Hair Cell Mitochondrial and Subsurface Cisternae Connectomics Are Candidate Mechanisms for Hearing Loss in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Pathology and mechanisms of cochlear aging.Journal of neuroscience research · 2020Review
- The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.Redox biology · 2020Article
- Increased burden of mitochondrial DNA deletions and point mutations in early-onset age-related hearing loss in mitochondrial mutator mice.Experimental gerontology · 2019Article
- Age-Related Hearing Loss.Cold Spring Harbor perspectives in medicine · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Mitochondrial DNA (mtDNA) mutations may contribute to aging and age-related diseases. Previously, we reported that accumulation of mtDNA mutations is associated with age-related hearing loss in mice carrying a mutator allele of the mitochondrial Polg DNA polymerase. To elucidate the role of mtDNA mutations in the pathogenesis of age-related hearing loss or presbycusis, we performed large scale gene expression analysis to identify mtDNA mutation-responsive genes and biological process categories associated with mtDNA mutations by comparing the gene expression patterns of cochlear tissues from 9-month-old mitochondrial mutator and control mice. mtDNA mutations were associated with transcriptional alterations consistent with impairment of energy metabolism, induction of apoptosis, cytoskeletal dysfunction, and hearing dysfunction in the cochlea of aged mitochondrial mutator mice. TUNEL staining and caspase-3 immunostaining analysis demonstrated that the levels of apoptotic markers were significantly increased in the cochleae of mitochondrial mutator mice compared to age-matched controls. These observations support a new model of how mtDNA mutations impact cochlear function whereby accumulation of mtDNA mutations lead to mitochondrial dysfunction, an associated impairment of energy metabolism, and the induction of an apoptotic program. The data presented here provide the first global assessment at the molecular level of the pathogenesis of age-related disease in mitochondrial mutator mice and reveal previously unrecognized biological pathways associated with mtDNA mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.