title: Mitochondrial point mutations do not limit the natural lifespan of mice.
abstract: Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate. Here, we use a new, highly sensitive assay to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 91895, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Vermulst
authors.forename: Jason H
authors.initials: JH
authors.lastname: Bielas
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Kujoth
authors.forename: Warren C
authors.initials: WC
authors.lastname: Ladiges
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rabinovitch
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Loeb
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000502:physiology*
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse