This research might be taken to illustrate the point that only some specific mutations in mitochondrial DNA (mtDNA) contribute to aging - those occurring in one of thirteen specific genes, per the SENS outline. So mice with accelerated mutation rates in all mitochondrial DNA exhibit accelerated aging, while mice with specific mitochondrial mutations that do not include those that contribute to aging do not exhibit accelerated aging.
It has been hypothesized that pathogenic mtDNA mutations that induce significant mitochondrial respiration defects cause mitochondrial diseases, and could also be involved in aging and age-associated disorders including tumor development. This hypothesis is partly supported by studies in mtDNA mutator mice: they possess a nuclear-encoded mtDNA polymerase with a defective proofreading function that leads to enhanced accumulation of random mutations in mtDNA with age, and the subsequent phenotypic expression of age-associated respiration defects and premature aging phenotypes, but not tumor development.
On the contrary, our previous studies showed that transmitochondrial mito-miceΔ carrying mtDNA with a large-scale deletion mutation (ΔmtDNA) expressed age-associated respiration defects, but not express the premature aging phenotypes. Similar results were obtained in other transmitochondrial mito-miceCOIM, which have an mtDNA point mutation in the COI gene. Recently, we generated new transmitochondrial mito-miceND6M, which have an mtDNA point mutation in the ND6 gene that is derived from Lewis lung carcinomas, and confers respiration defects and overproduction of reactive oxygen species (ROS). Mito-miceND6M did not express premature aging phenotypes, but were prone to B-cell lymphoma development. Thus, it appears to be discrepant that premature aging phenotypes are exclusively observed in mtDNA mutator mice, but not in transmitochondrial mito-mice even though they all express mitochondrial respiration defects caused by mutated mtDNA.