There is substantial agreement among interspecies estimates of DNA repair activity

Abstract

Faithful maintenance of the genetic material is essential for cellular and organismal function. Thus the activity with which nuclear and mitochondrial DNA is repaired in somatic cells is likely to be an crucial determinant of maximal lifespan (MLS). However there has been controversy over both the actual rates of DNA repair in a variety of species, and the correlation of those rates with maximal lifespan. Five comparative studies of DNA repair have been re-analyzed with reference to an internal repair standard. Although some variance in measurements of DNA repair activity of the same species in different laboratories was observed, overall there is good agreement on the rank order of repair activity once those studies are internally calibrated. A six-fold range of relative DNA repair activity was observed, with mouse, rat and shrew lowest (0.9 to 1.0), and human and gorilla highest (4.5 to 5.3). The correlation between DNA repair activity and MLS was good, but not excellent (r2 = 0.845); a possible explanation is that active DNA repair is a necessary but not sufficient condition for long MLS. We investigated the kinetics of mitochondrial mutagenesis and tumorigenesis in mice and humans, and observed that each proceeds at a rate approximately 40-fold faster in mice than in humans. Thus one likely consequence of the deficiency of DNA repair in small rodents is an increased rate of mutagenesis and tumorigenesis. The large differences in metabolic investment in genomic maintenance in mice versus humans is a prediction of the disposable soma theory of aging, which is discussed.