The role of DNA damage and repair in aging through the prism of Koch-like criteria

Since the first publication on Somatic Mutation Theory of Aging (Szilárd, 1959), a great volume of knowledge in the field has been accumulated. Here we attempted to organize the evidence “for” and “against” the hypothesized causal role of DNA damage and mutation accumulation in aging in light of four Koch-like criteria. They are based on the assumption that some quantitative relationship between the levels of DNA damage/mutations and aging rate should exist, so that (i) the longer-lived individuals or species would have a lower rate of damage than the shorter-lived, and (ii) the interventions that modulate the level of DNA damage and repair capacity should also modulate the rate of aging and longevity and vice versa. The analysis of how the existing data meets the proposed criteria showed that many gaps should still be filled in order to reach a clear-cut conclusion. As a perspective, it seems that the main emphasis in future studies should be put on the role of DNA damage in stem cell aging.

► Accumulation of DNA damage/mutations has long been suggested to play a causal role in aging.
► Four logical “Koch-like” criteria are proposed for evaluating this hypothesis.
► They presume some quantitative relationship between the levels of DNA damage and aging rate.
► The analysis showed that many gaps should still be filled in order to reach a clear-cut conclusion.