The size of the contribution of stochastic nuclear DNA damage to aging is debated. It causes cancer, when rare combinations of cancerous mutations occur and suppression of those early cancerous cells fails, but can it give rise to a meaningful degree of tissue dysfunction otherwise? The present consensus is that most such damage is irrelevant, occurring in cells that will not replicate further all that many times, and in genes that are not active. However, mutations in stem cells and progenitor cells can spread widely throughout tissue. Indeed, evidence shows that mice and humans exhibit a patterning of such distributed mutations. No robust evidence yet exists to pin down a size of effect of this spread of mutations on the progression of aging, however.

There are many ways in which DNA can become damaged, and cells possess highly efficient DNA repair mechanisms that quickly fix almost all issues. In today's open access paper, researchers show that the damage that occurs during replication of DNA does not have a significant influence on aging in mammals, despite the fact that it does appear to affect aging in short-lived lower species. The researchers engineered mice to improve repair of replicative DNA damage, but these mice did not live longer as a result. This is an interesting addition to the debate over the relevance of stochastic DNA damage to aging.

Supraphysiological protection from replication stress does not extend mammalian lifespan