Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease
Abstract
Oxidative damage to mitochondrial DNA (mtDNA) increases with age in the brain and can induce G:C to T:A and T:A to G:C point mutations. Though rare at any particular site, multiple somatic mtDNA mutations induced by oxidative damage or by other mechanisms may accumulate with age in the brain and thus could play a role in aging and neurodegenerative diseases. However, no prior study has quantified the total burden of mtDNA point mutation subtypes in the brain. Using a highly sensitive cloning and sequencing strategy, we find that the aggregate levels of G:C to T:A and T:A to G:C transversions and of all point mutations increase with age in the frontal cortex (FCtx). In the substantia nigra (SN), the aggregate levels of point mutations in young controls are similar to the levels in the SN or FCtx of elderly subjects. Extrapolation from our data suggests an average of 2.7 (FCtx) to 3.2 (SN) somatic point mutations per mitochondrial genome in elderly subjects. There were no significant differences between Parkinson's disease (PD) patients and age-matched controls in somatic mutation levels. These results indicate that individually rare mtDNA point mutations reach a high aggregate burden in FCtx and SN of elderly subjects.
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High levels of somatic mtDNA point mutations were identified in elderly PD patients.
“We also identified high levels of somatic mtDNA point mutations in elderly PD patients20.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [20]
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- Authors
- Simon, D. K., Lin, M. T., Zheng, L., Liu, G.-J., Ahn, C. H., Kim, L. M., Mauck, W. M., Twu, F., Beal, M. F., & Johns, D. R.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Cornell University (US)
- Corresponding author
- Simon, David K
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 25
- Issue
- 1
- Pages
- 71-81
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2075132953
- Cited by
- 118
- References
- 64
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k24ns002239-05, 5k08ns001971-03, 5k08ag000798-03)
- National Institute on Aging (R01AG20729, R01AG020729, K08-AG00798)
- National Institute of Neurological Disorders and Stroke (K08 NS01971, K24 NS02239, K02 NS4311-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- somatic mitochondrial DNA mutations, mitochondrial DNA point mutations, oxidative damage, brain aging, Parkinson's disease, frontal cortex, substantia nigra, transversions, mutational burden, neurodegeneration
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Cell Line, Child, Child, Preschool, DNA Mutational Analysis, DNA, Mitochondrial, Female, Frontal Bone, Humans, Infant, Male, NADH Dehydrogenase, Parkinson Disease, Substantia Nigra, Case-Control Studies, Polymerase Chain Reaction, Point Mutation, Sequence Analysis, DNA
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