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Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication

Michikawa, Yuichi and Mazzucchelli, Franca and Bresolin, Nereo and Scarlato, Guglielmo and Attardi, Giuseppe (1999) Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication. Science, 286 (5440). pp. 774-779. ISSN 0036-8075. doi:10.1126/science.286.5440.774.

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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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Additional Information:© 1999 American Association for the Advancement of Science. Received 26 March 1999; accepted 14 September 1999. Supported by National Institute on Aging (NIH) grant AG12117-03 (to G.A.). We thank A. Chomyn and G. Villani for valuable discussions, M. Lai for support, A. Aman, R. Steinberger, and M. Scott for their help with experiments, and A. Drew, B. Keeley, R. Zedan, and C. Lin for expert technical assistance.
Funding AgencyGrant Number
National Institute on AgingAG12117-03
Issue or Number:5440
Record Number:CaltechAUTHORS:20141124-090813433
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52086
Deposited By: Tony Diaz
Deposited On:24 Nov 2014 21:30
Last Modified:10 Nov 2021 19:20

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