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Science 22 October 1999:
Vol. 286. no. 5440, pp. 774 - 779
DOI: 10.1126/science.286.5440.774
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Reports

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

Yuichi Michikawa, 1 Franca Mazzucchelli, 2 Nereo Bresolin, 2 Guglielmo Scarlato, 2 Giuseppe Attardi *1

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.

1 Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
2 University of Milan, Institute of Clinical Neurology, Dino Ferrari Center, IRCCS, and Ospedale Maggiore di Milano-Policlinico, IRCCS E. Medea-Bosisio Parini (LC), 20122 Milan, Italy.
*   To whom correspondence should be addressed. E-mail: attardig{at}seqaxp.bio.caltech.edu

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