Timo E. S. Kauppila, Ana Bratic, Martin Borch Jensen, Francesca Baggio, Linda Partridge, Heinrich Jasper, Sebastian Grönke, and Nils-Göran Larsson
- The authors engineered fruit flies expressing mutant versions of mitochondrial DNA polymerase as a means to introduce mtDNA mutations. This model is analogous to the 'mutator mouse', which shows premature ageing phenotypes.
- The authors did not observe an increase in levels of somatic mtDNA mutations with age in the thorax of these mutant fruit flies, suggesting low mtDNA turnover (relative to total lifespan) in this tissue. However, old female flies tranmit more mtDNA mutations than young female flies, suggesting that mtDNA mutations may accumulate in proliferative tissues such as the female gonads.
- Moderately increasing the somatic mtDNA mutation load did not have any impact on fly lifespan or physiology
- Even after multiple generations, flies showed high tolerance to mtDNA mutations. The authors suggest this is likely due to the relatively large mtDNA genetic bottleneck during fly development
- Very high levels of mtDNA mutation caused sensitivity to mechanical and starvation stress, intestinal stem cell dysfunction, and reduced lifespan
- Flies with 9.7×10−4 mutations per bp had similar lifespans to WT flies, whereas mice with 2.1×10−4 mutations per bp display shortened lifespan.