Aix, EstherGutierrez-Gutierrez, OscarSanchez-Ferrer, CarlotaAguado, TaniaFlores, Ignacio2017-10-302017-10-302016J Cell Biol. 2016; 213(5):571-830021-9525http://hdl.handle.net/20.500.12105/5221The 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.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/MOUSE HEARTTERMINAL TRANSFERASECARDIAC REGENERATIONOXIDATIVE STRESSMAMMALIAN HEARTSTEM-CELLSPROLIFERATIONEXPRESSIONCANCERMICEAtribución-NoComercial-CompartirIgual 4.0 Internacional27241915213571-58310.1083/jcb.2015100911540-8140Journal of Cell Biologyopen access