Two methods to induce clean DSBs provide tools to dissect the age-related consequences stemming from DSBs alone. The first method induces DSBs via adenoviral delivery of a restriction enzyme, SacI, which is under control of tetracycline and tamoxifen (White et al., 2015). The second method, a transgenic mouse model, induces DSBs conditionally using the I-PpoI restriction enzyme fused to GFP under control of tamoxifen, and in a tissue-specific manner using Cre recombinase (Kim et al., 2015).