Response to: The information theory of aging has not been tested

Timmons et al. question whether cell elimination might be a contributing cause of the progeroid phenotype in inducible changes to the epigenome (ICE) mice. We have found no evidence that this is the case. We specifically designed our tamoxifen (TAM)-induction protocols to ensure that endonuclease expression was at a low level such that DNA cutting by I-PpoI was infrequent and did not cause cells to experience cell-cycle arrest or apoptosis. By assessing protein localization, transcriptomics, DNA damage markers, and cell death assays, we were unable to detect any acute DNA damage, overt DNA damage responses, cell death, or cell elimination, either during or after induction of I-PpoI, in the ICE mice.