The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
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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“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]
Citations
Cites
Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,740
Oxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R. S., Sherer, T., MacKenzie, G. M., Garcia‐Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,777
Mitochondrial Complex I Deficiency in Parkinson's Disease
Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb02325.x · Cited by 2,283
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., & Loeb, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48474-8 · Cited by 1,844
The substantia nigra of the human brain
Damier, P., Hirsch, É. C., Agid, Y., & Graybiel, A. M. (1999) · Brain · doi:10.1093/brain/122.8.1437 · Cited by 1,827
MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
Schapira, A. H. V., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., Clark, J. B., & MARSDEN, C. D. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92366-0 · Cited by 1,757
Normal oxidative damage to mitochondrial and nuclear DNA is extensive.
Richter, C., Park, J. W., & Ames, B. N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6465 · Cited by 1,730
Kasai, H. (1997) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(97)00035-5 · Cited by 1,157
Research works printed but not linked: 2
- Chen, 1994, Evidence for impairment of energy metabolism in Parkinson’s disease using in vivo localized MR spectroscopy, Proc. Soc. Mag. Res., 1, 194
- Sanchez-Ramos, 1994, A marker of oxyradical-mediated DNA damage (8-hydroxy-2′-deoxyguanosine) is increased in nogr-striatum of Parkinson’s disease, Neurodegeneration, 3, 197
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Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Self-citationOxidative Stress: A Key Modulator in Neurodegenerative Diseases
Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019) · Molecules · doi:10.3390/molecules24081583 · Cited by 2,398
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061
Mitochondrial dysfunction in Parkinson's disease
Bose, A., & Beal, M. F. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13731 · Cited by 915
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Metadata
- 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 › Clinical 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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