title: Transcription could be the key to the selection advantage of mitochondrial deletion mutants in aging.
abstract: 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.
authors.affiliation: Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors.forename: Axel
authors.initials: A
authors.lastname: Kowald
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
mesh_terms: D000375:Aging / Q000378:metabolism*; D003198:Computer Simulation; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D017384:Sequence Deletion / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial
keywords: mathematical model; mitochondrial mutations