Cardiomyocyte Telomere Damage

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  • Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.
  • Maggiorani D, Berlinguer-Palmini R, Greaves LC, Mialet-Perez J, Richardson GD, Passos JF
  • The EMBO journal , 2/ 2019
  • Ageing Research Laboratories, Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
  • Ageing is the biggest risk factor for cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening, has been implicated in age-related tissue dysfunction. Here, we address the question of how senescence is induced in rarely dividing/post-mitotic cardiomyocytes and investigate whether clearance of senescent cells attenuates age-related cardiac dysfunction. During ageing, human and murine cardiomyocytes acquire a senescent-like phenotype characterised by persistent DNA damage at telomere regions that can be driven by mitochondrial dysfunction and crucially can occur independently of cell division and telomere length. Length-independent telomere damage in cardiomyocytes activates the classical senescence-inducing¬†pathways, p21CIP and p16INK4a, and results in a non-canonical¬†senescence-associated secretory phenotype, which is pro-fibrotic and pro-hypertrophic. Pharmacological or genetic clearance of senescent cells in mice alleviates detrimental features of cardiac ageing, including myocardial hypertrophy and fibrosis. Our data describe a mechanism by which senescence can occur and contribute to age-related myocardial dysfunction and in the wider setting to ageing in post-mitotic tissues.
Rahuman Sheriff, Carole Proctor

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  • Model originally submitted by : Carole Proctor
  • Submitted: Feb 7, 2019 4:34:28 PM
  • Last Modified: Feb 14, 2019 4:56:10 PM
  • Version: 4 public model Download this version
    • Submitted on: Feb 14, 2019 4:56:10 PM
    • Submitted by: Rahuman Sheriff
    • With comment: PubMed ID and publication details updated
  • Version: 3 public model Download this version
    • Submitted on: Feb 7, 2019 4:34:28 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Edited model metadata online.