Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts
Abstract
Some mutations in mitochondrial DNA (mtDNA) causing a number of neuromuscular diseases are suggested to arise spontaneously during the life of an individual. To substantiate the extent and the rate of these somatic mutations, mtDNA specimens from post-mortem human heart muscles of subjects in differing age groups were hydrolyzed. 8-Hydroxy-deoxyguanosine (8-OH-dG), a hydroxyl-radical adduct of deoxyguanosine, in mtDNA, was quantitatively determined using a micro high-performance liquid chromatography/mass spectrometry system. In each specimen, the mtDNA with a 7.4 kilo base-pair deletion was quantified by the kinetic polymerase chain reaction method. In association with age, the 8-OH-dG content accumulated exponentially up to 1.5% with a correlative increase in the content of the deleted mtDNA up to 7%. Clear correlation between the 8-OH-dG content in mtDNA and the population of mtDNA with a deletion (r = 0.93, P < 0.01) gives insight into the mechanism for the generation of a large deletion. These results indicate that accumulation of somatically acquired oxygen damage together with age-associated mutations in mtDNA which lead to bioenergetic deficiency and the heart muscle weakness are inevitable in human life.
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Correlative evidence between increased levels of 8-oxo-dG and age-related deletions in mtDNA from humans, mice, rats and houseflies has been reported.
“Correlative evidence between increased levels of 8-oxo-dG and age-related deletions in mtDNA from humans (Capel et al., 2005; Hayakawa et al., 1992; Hayakawa et al., 1991), mice (Vermulst et al., 2007), rats (Sawada and Carlson, 1987) and houseflies (Sohal and Sohal, 1991) has been reported.”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Hayakawa et al., 1992
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Background
- Authors
- Hayakawa, M., Hattori, K., Sugiyama, S., & Ozawa, T.
- Affiliations
- Nagoya University (JP)
- ORCID
- Ozawa, Takayuki
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1992-12
- Volume
- 189
- Issue
- 2
- Pages
- 979-985
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2057162464
- Cited by
- 283
- References
- 11
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 6 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 1 · 2013: 7 · 2012: 3
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- mitochondrial DNA mutations, somatic mutations, aging, 8-hydroxy-2'-deoxyguanosine, hydroxyl radical adducts, oxidative DNA damage
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Chromatography, High Pressure Liquid, Deoxyguanosine, DNA Damage, DNA, Mitochondrial, Female, Heart, Humans, Male, Middle Aged, Mitochondria, Heart, Models, Genetic, Molecular Sequence Data, Oxygen, Mass Spectrometry, Point Mutation, Sequence Deletion
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