Aix, EstherGutiérrez-Gutiérrez, ÓscarSánchez-Ferrer, CarlotaAguado Sánchez, TaniaFlores, Ignacio2023-12-192023-12-192016Esther Aix, Óscar Gutiérrez-Gutiérrez, Carlota Sánchez-Ferrer, Tania Aguado, Ignacio Flores; Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation. J Cell Biol 6 June 2016; 213 (5): 571–583. doi: https://doi.org/10.1083/jcb.2015100910021-952510.1083/jcb.201510091https://hdl.handle.net/20.500.14352/91537The molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc−/−) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc−/− newborns but rescued in G3 Terc−/−/p21−/− mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts.engAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/journal article1540-8140https://rupress.org/jcb/article/213/5/571/38346/Postnatal-telomere-dysfunction-inducesopen access577.2Cell cycle and divisionDNA biologyCiencias Biomédicas24 Ciencias de la Vida