Mitochondrial point mutations do not limit the natural lifespan of mice.
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.
Vermulst
Marc
M
Department of Pathology, University of Washington, Seattle, Washington 91895, USA.
Bielas
Jason H
JH
Kujoth
Gregory C
GC
Ladiges
Warren C
WC
Rabinovitch
Peter S
PS
Prolla
Tomas A
TA
Loeb
Lawrence A
LA
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*
D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse