title: Maternally transmitted mitochondrial DNA mutations can reduce lifespan.
abstract: We recently showed that germline transmission of mitochondrial DNA mutations via the oocyte cause aggravation of aging phenotypes in prematurely aging mtDNA mutator (PolgA(mut/mut)) mice. We discovered that 32% of these mice also exhibit stochastic disturbances of brain development, when maternal mtDNA mutations were combined with homozygosity for the PolgA mutation, leading to de novo somatic mtDNA mutations. Surprisingly, we also found that maternally transmitted mtDNA mutations can cause mild premature aging phenotypes also in mice with a wild-type nuclear DNA background. We now report that in addition to the early onset of aging phenotypes, these mice, burdened only by low levels of mtDNA mutations transmitted via the germline, also exhibit reduced longevity. Our data thus demonstrate that low levels of maternally inherited mtDNA mutations when present during development can affect both overall health and lifespan negatively.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Ross
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Coppotelli
authors.affiliation: Department of Neurosurgery, University Hospitals, Case Western Reserve Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Hoffer
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D018095:Germ-Line Mutation; D008136:Longevity / Q000235:genetics*; D051379:Mice; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse