Mitochondrial point mutations do not limit the natural lifespan of mice

Nat Genet. 2007 Apr;39(4):540-3. doi: 10.1038/ng1988. Epub 2007 Mar 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Animals
  • Cells, Cultured
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Longevity / genetics*
  • Mice
  • Mice, Transgenic
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Point Mutation / physiology*

Substances

  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • Polg protein, mouse