Cited by 118Mitochondrial Function and PathologyParkinson's Disease Mechanisms and TreatmentsGenetics, Aging, and Longevity in Model Organisms

Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease

Simon, David K, Lin, Michael T, Zheng, Leiya, Liu, Guang-Jun, Ahn, Colette H, Kim, Lauren M, Mauck, William M, Twu, Florence +2 more·2004·Neurobiology of Aging

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.

Integrity signals

Registry

Crossref · 10.1016/s0197-4580(03)00037-x

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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]

Cites

Flagged first, then by citations

1 of the 64 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review