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Lookup NU author(s): Dr Axel Kowald, Emeritus Professor Thomas Kirkwood
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The mitochondrial theory of aging is widely popular but confronted by several apparent inconsistencies. On the one hand, mitochondrial energy production is of central importance to the health and proper functioning of cells, and single-cell studies have shown that mtDNA deletion mutants accumulate in a clonal fashion in various mammalian species, displacing the wild-type mtDNAs. On the other hand, no explanation exists yet for the clonal expansion of mtDNA mutants that is compatible with experimental observations. We present here a new idea based on the distinctive connection between transcription and replication of metazoan mtDNA. Bioinformatic analysis of mtDNA deletion spectra strongly supports the predictions of this hypothesis and identifies specific candidates for proteins involved in transcriptional control of mtDNA replication. Computer simulations show the mechanism to be compatible with the available data from short-and long-lived mammalian species.
Author(s): Kowald A, Kirkwood TBL
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2014
Volume: 111
Issue: 8
Pages: 2972-2977
Print publication date: 03/02/2014
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: http://dx.doi.org/10.1073/pnas.1314970111
DOI: 10.1073/pnas.1314970111
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