Impact of Endogenous Genomic Damage on Adult Stem Cells and Tissue Homeostasis

We present important findings linking DNA repair pathways with stem cell exhaustion during ageing, as well as in specific cancer-related mutational patterns. Moreover, we put forward a general model, in which remaining cellular lifespan determines which DNA damage response strategy is used by the cell.
Such a model provides an explanation for the segmental ageing phenotypes of human progeroid syndromes and DNA repair-deficient corresponding mouse mutants, as well as the different aging trajectories between organs and tissues during natural ageing.