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. 2023 Mar 27;8:140. doi: 10.1038/s41392-023-01412-9

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Diagram and molecular mechanisms underlying the ICE mouse models. a left, the Inducible Change to the Epigenome (ICE) system. In this gene-engineering mouse model, recombined protein of endonuclease I-PpoI and Cre-ER^T2 is under control of tamoxifen. If tamoxifen is added, I-PpoI will enter nucleus to create DNA double strand break which then will be repaired through faithful DNA repair pathway. right, aging phenotypes of ICE models. b Epigenetic landscapes changes in ICE model, including the erosion of H3K27ac, remodeling chromatin contact, and aberrant super enhancers. c The diagram of cell rejuvenation. Briefly, overexpression Oct4/Sox2/Klf4 in ICE/old mouse cells can recover youthful cell transcriptome