In ageing research, mitochondria have been scrutinized by researchers for a long time already. The mitochondria in a cell contain thousand of copies of a circular DNA genome. These encode, for instance, proteins that are important for the enzymes of the respiratory chain. Whereas the DNA within the nucleus comes from both parents, the mitochondrial DNA only includes maternal genes, as mitochondria are transmitted to offspring via the oocyte and not via sperm cells. As the numerous DNA molecules within a cell's mitochondria mutate independently from each other, normal and damaged mtDNA molecules are passed to the next generation.
To examine which effects mtDNA damage exerts on offspring, researchers used a mouse model. Mice that inherited mutations of mtDNA from their mother not only died quicker compared to those without inherited defects, but also showed premature ageing effects like reduced body mass or a decrease in male's fertility. Moreover, these rodents were prone to heart muscle disease.
As the researchers discovered, mutations of mtDNA not only can accelerate ageing but also impair development: In mice that, in addition to their inherited defects, accumulated mutations of mtDNA during their lifetime, researchers found disturbances of brain development. They conclude that defects of mtDNA that are inherited and those that are acquired later in life add up and finally reach a critical number.
"Our findings shed light on the ageing process and strongly suggest that the mitochondria play a key role in ageing. They also show that it is important to reduce the number of mutations," says Larsson. However, the question of whether it is possible to affect the degree of mtDNA damage through, for example, lifestyle intervention is yet to be investigated. In the future, the scientists want to investigate whether a reduced number of mutations can actually increase lifespan in model organisms such as fruit flies and mice.
|Contact: Nils-Göran Larsson|