Comparative genomics of aging

Genomes are inherently unstable as a consequence of their role as substrate for evolutionary change. In somatic cells the accumulation of both mutations and epimutations are the inevitable outcome of errors made during DNA replication or the repair of DNA damage. Genome instability has often been considered as a universal cause of aging, with genome maintenance as the main determinant of species-specific life span. It has been very difficult to test this hypothesis directly because of a lack of good model systems allowing a direct comparison of the rate of spontaneous genome alteration in somatic tissues during aging. Here we review the results of a direct comparison of spontaneous DNA mutation frequencies in somatic tissue of mice and fruit flies using transgenic mutational reporter genes.