Do mtDNA deletions drive premature aging in mtDNA mutator mice?
Deletions in mitochondrial DNA (mtDNA) have long been suspected to be involved in mammalian aging, but their role remains controversial. Recent research has demonstrated that relatively higher levels of mtDNA deletions correlate with premature aging in mtDNA mutator mice, which led to the conclusion that premature aging in these mice is driven by mtDNA deletions. However, it is reported here that the absolute level of deletions in mutator mice is quite low, especially when compared with the level of point mutations in these mice. It is thus argued that the available data are insufficient to conclude that mtDNA mutations drive premature aging in mtDNA mutator mice. It remains possible that clonal expansion of mtDNA deletions may result in sufficiently high levels to play a role in age-related dysfunction in some cells, but assessing this possibility will require studies of the distribution of these deletions among different cell types and in individual cells.
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, United States.
Yevgenya
Y
Kraytsberg
David K
DK
Simon
Douglas M
DM
Turnbull
Konstantin
K
Khrapko
D019588:Aging, Premature / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse