Maintenance of genome sequence integrity in long- and short-lived rodent species
Lei Zhang, Xiao Dong, Xiao Tian, Moonsook Lee, Julia Ablaeva, Denis Firsanov, Sang‐Goo Lee, Alexander Y. Maslov, Vadim N. Gladyshev, Andrei Seluanov, Vera Gorbunova, Jan Vijg
Abstract
DNA mutations in somatic cells have been implicated in the causation of aging, with longer-lived species having a higher capacity to maintain genome sequence integrity than shorter-lived species. In an attempt to directly test this hypothesis, we used single-cell whole-genome sequencing to analyze spontaneous and bleomycin-induced somatic mutations in lung fibroblasts of four rodent species with distinct maximum life spans, including mouse, guinea pig, blind mole-rat, and naked mole-rat, as well as humans. As predicted, the mutagen-induced mutation frequencies inversely correlated with species-specific maximum life span, with the greatest difference observed between the mouse and all other species. These results suggest that long-lived species are capable of processing DNA damage in a more accurate way than short-lived species.