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Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication
Abstract
Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
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Cites
Progressive Increase of the Mutated Mitochondrial DNA Fraction in Kearns-Sayre Syndrome
Larsson, N.-G., Holme, E., Kristiansson, B., Oldfors, A., & Tulinius, M. (1990) · Pediatric Research · doi:10.1203/00006450-199008000-00011 · Cited by 324
Cited by
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
Mitochondrial control of cell death
Kroemer, G., & Reed, J. C. (2000) · Nature Medicine · doi:10.1038/74994 · Cited by 3,103
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987
Halliwell, B. (2001) · Drugs & Aging · doi:10.2165/00002512-200118090-00004 · Cited by 1,502
Metadata
- Authors
- Michikawa, Y., Mazzucchelli, F., Bresolin, N., Scarlato, G., & Attardi, G.
- Venue
- Science
- Published
- 1999-10-22
- Volume
- 286
- Issue
- 5440
- Pages
- 774-779
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2074303856
- Cited by
- 725
- References
- 1
- FWCI
- 15.01
- Type
- journal article
- Language
- en
- Open access
- closed
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- Michikawa, Y., Mazzucchelli, F., Bresolin, N., Scarlato, G., & Attardi, G. (1999). Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication. Science. https://doi.org/10.1126/science.286.5440.774
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
