A mother’s genes influence her child’s ageing

Mutations of mitochondrial DNA can hasten offspring’s ageing process

As we grow older, not only the function of organs slows down. Also on a cellular level more and more damages occur. One reason is that DNA errors accumulate which cause defective cells. Now a team of researchers lead by Nils-Göran Larsson at the Max Planck Institute for Biology of Ageing in Cologne has shown that ageing is determined not only by the accumulation of DNA damage that occurs during lifetime but also by damage that we acquire from our mothers. In a study on mice, the researchers have shown that mutations of maternally inherited mitochondrial DNA influence the offspring’s ageing process starting from birth.

Ageing is a complex process, in the course of which more and more damage accumulates within the bodies’ tissues, cells and molecules – with serious consequences: Organs lose their function and mortality risk increases. Why some people age faster than others has many reasons that are still unsolved. However, damage that occurs within the mitochondria – the cell’s powerhouses – seems to be of particular importance for ageing.

“The mitochondrion contains its own DNA, the so-called mitochondrial DNA or mtDNA, which changes faster than the DNA in the nucleus, and this has a significant impact on the ageing process,” says Nils-Göran Larsson, Director at the Max Planck Institute for Biology of Ageing in Cologne and scientist at the Karolinska Institute in Stockholm. Together with Lars Olson, also a scientist at the Karolinska Institute, he has led the study.

“Many mutations in the mitochondria gradually disable the cell’s energy production.” Contrary to previous findings, not only mutations that accumulate during lifetime play a role: “Surprisingly, we discovered that our mother’s mitochondrial DNA seems to influence our own ageing,” says James Stewart, a researcher in Larsson’s department. “If mice inherit mtDNA with mutations from their mother, they age more quickly.” Thus, some of the mutations that cause ageing are already present at birth.

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.