Erratum: Loss of epigenetic information as a cause of mammalian aging (Cell (2023) 186(2) (305–326.e27), (S0092867422015707), (10.1016/j.cell.2022.12.027))

(Cell 186, 305–326.e1–e14; January 19, 2023) Our paper used a system called “ICE” (inducible changes to the epigenome) to study whether a loss of epigenetic information leads to aging and whether the expression of a subset of Yamanka factors can reverse these age-associated changes, as tests of the Information Theory of Aging. We provide additional information about our experimental design and reference previous, relevant papers from our group and others that had not been cited in the original submission. We apologize for any confusion that may have arisen due to this information not being available in the original published paper. In our Correction, we add details about the transgenic construct design, tamoxifen administration, and temporal and spatial control of I-PpoI in the Results, Discussion, and STAR Methods sections. Our I-PpoI papers looking at the genotoxic stress response in DNA-damage-sensitive cell types have been referenced. The article has now been corrected online, and the corrected texts are provided below. In the Results section, the original sentence read: “To test our hypothesis in vivo, we performed whole-body I-PpoI expression in 4- to 6-month-old mice for 3 weeks (Figure 1L).” The corrected sentence now reads: “To test our hypothesis in vivo, we performed whole-body I-PpoI expression in 4- to 6-month-old mice for 3 weeks by providing TAM in the diet, rather than TAM intraperitoneal injections, to limit the amount of I-PpoI expressed so genotoxic stress would not arise (Figure 1L).” In the Discussion section, the original sentence read: “…In this paper, we show that non-mutagenic DSB repair…” The corrected sentence now reads: “…In our previous studies, TAM was administered via intraperitoneal injection, leading to significantly elevated TAM levels compared to TAM feeding (Smith et al., 2022), along with increased I-PpoI expression within the nucleus. We examined cells that were highly sensitive to DNA damage to study the genotoxic stress response (Kato et al., 2021; Kim et al., 2016). In this paper, we used a mouse feeding protocol that induced minimal nuclear I-PpoI expression and observed no signs of genotoxic stress. We show that non-mutagenic DSB repair…” In the STAR Methods section, the original sentence read: “4- to 6-month-old Cre and ICE mice were fed a modified AIN-93G purified rodent diet with 360 mg/kg tamoxifen citrate for 3 weeks to carry out I-PpoI induction.” The corrected sentence now reads: “4- to 6-month-old Cre and ICE mice were fed a modified AIN-93G purified rodent diet with 360 mg/kg tamoxifen citrate for 3 weeks to carry out I-PpoI induction. A weak promoter drives a single copy of the I-PpoI gene per cell. When mice are fed tamoxifen (TAM) chow, minimal I-PpoI expression is observed within the nucleus, accompanied by rapid degradation of I-PpoI upon withdrawal of TAM. This precise temporal and spatial regulation of I-PpoI is intended to yield negligible genotoxicity and cell death, which was confirmed by TUNEL staining and analyses of caspase-3 cleavage and levels of p-ATM, p-p53, γH2AX, and hippocampal neurodegeneration during and after TAM treatment.” The additional references added are presented below: • Kato, T., Liu, N., Morinaga, H., Asakawa, K., Muraguchi, T., Muroyama, Y., Shimokawa, M., Matsumura, H., Nishimori, Y., Tan, L.J., et al. (2021). Dynamic stem cell selection safeguards the genomic integrity of the epidermis. Developmental Cell 56, 3309–3320.e3305. https://doi.org/10.1016/j.devcel.2021.11.018.• Kim, J., Sturgill, D., Tran, A.D., Sinclair, D.A., and Oberdoerffer, P. (2016). Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability. Nucleic Acids Research 44, e64. https://doi.org/10.1093/nar/gkv1482.• Smith, B.M., Saulsbery, A.I., Sarchet, P., Devasthali, N., Einstein, D., and Kirby, E.D. (2022). Oral and Injected Tamoxifen Alter Adult Hippocampal Neurogenesis in Female and Male Mice. eNeuro 9. https://doi.org/10.1523/eneuro.0422-21.2022.