Our DNA accumulates damage as we age. It is very clear that mitochondrial DNA damage is important in aging, putting efforts to develop mitochondrial repair biotechnologies high on the priority list, but is the accumulation of nuclear DNA damage also important in aging?
It is well settled that the level of nuclear DNA damage and mutation exhibited by an organism rises over time. It is also well settled that higher levels of nuclear DNA damage and mutation mean a greater cancer risk - this is one of the reasons why cancer is predominantly a disease of the old. The more cells that suffer DNA damage, the more likely it is that one or more cells experience exactly the type of damage needed to run amok as the self-replicating seeds to a cancer. But is nuclear DNA damage and mutation a cause of aging?
That increasing instability of the genome contributes to age-related degeneration is the present working assumption for much of the aging research community, but this hypothesis is not unchallenged. The lack of a definitive proof is one problem: there is no good experiment to show that reduction in nuclear DNA damage levels - and only nuclear DNA damage levels - extends life.
It is quite possible that over a normal human life span, nuclear DNA damage gives rise to cancer and not much else of significance. Equally, maybe it does have a larger role. But to answer the question one way or another, we need to see an experiment that shows extended life in mammals directly resulting from reduced levels of nuclear DNA damage.
Here is an example of new research that might lead to that experiment:
a process called acetylation regulates the maintenance of our DNA [and] determines the degree of fidelity of both DNA replication and repair. The finding builds on past research, which established that as humans evolved, we created two routes for DNA replication and repair - a standard route that eliminates some damage and a moderate amount of errors, and an elite route that eliminates the large majority of damage and errors from our DNA.
Only the small portion of our DNA that directs the creation of all the proteins we are made of - proteins in blood cells, heart cells, liver cells and so on - takes the elite route, which uses much more energy and so "costs" the body more. The remaining majority of our DNA, which is not responsible for creating proteins, takes the standard route, which requires fewer resources. ... acetylation directs which proteins take which route, favoring the protection of DNA that creates proteins by shuttling them down the elite, more accurate course.
"If we found a way to improve the protection of DNA that guides protein production, basically boosting what our body already does to eliminate errors, it could help us live longer. A medication that would cause a small alteration in this acetylation-based regulatory mechanism might change the average onset of cancers or neurological diseases to well beyond the current human lifespan."
A long drug discovery process lies between knowing these biochemical mechanisms and being able to manipulate them - but being able to manipulate the fidelity of DNA repair offers the possibility of directly establishing in mammals the degree to which nuclear DNA damage contributes to degenerative aging.