{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xml":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1608250001?filename=MODEL1608250001_url.xml"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Carole Proctor"],"curationStatus":["Non-curated"],"levelVersion":["L2V3"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL1608250001"],"publication_pubmed":["30737259"],"isPrivate":["false"],"repository":["BioModels"],"omics_type":["Models"],"modelFormat":["SBML"],"tokenised_name":["Cardiomyocyte Telomere Damage by ROS without Cell Division"],"publication_year":["2019"],"submissionId":["MODEL1608250001"],"publication_authors":["Rhys Anderson, Anthony Lagnado, Damien Maggiorani, Anna Walaszczyk, Emily Dookun, James Chapman, Jodie Birch, Hanna Salmonowicz, Mikolaj Ogrodnik, Diana Jurk, Carole Proctor, Clara Correia-Melo, Stella Victorelli, Edward Fielder, Rolando Berlinguer-Palmini, Andrew Owens, Laura C Greaves, Kathy L Kolsky, Angelo Parini, Victorine Douin-Echinard, Nathan K LeBrasseur, Helen M Arthur, Simon Tual-Chalot, Marissa J Schafer, Carolyn M Roos, Jordan D Miller, Neil Robertson, Jelena Mann, Peter D Adams, Tamara Tchkonia, James L Kirkland, Jeanne Mialet-Perez, Gavin D Richardson, João F Passos"],"first_author":["Rhys Anderson"],"publication":["30737259,\n                            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, p21<sup>CIP</sup> and p16<sup>INK4a</sup>, 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.. 5, 38.\n                            Ageing Research Laboratories, Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK."],"submitter_mail":["carole.proctor@ncl.ac.uk"],"submitter_affiliation":["Newcastle University"],"pubmed_abstract":["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, p21<sup>CIP</sup> and p16<sup>INK4a</sup>, 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."],"pubmed_title":["Length-independent telomere damage drives post-mitotic cardiomyocyte senescence."],"pubmed_authors":["Anderson Rhys R, Lagnado Anthony A, Maggiorani Damien D, Walaszczyk Anna A, Dookun Emily E, Chapman James J, Chapman James J, Birch Jodie J, Salmonowicz Hanna H, Ogrodnik Mikolaj M, Jurk Diana D, Proctor Carole C, Correia-Melo Clara C, Victorelli Stella S, Fielder Edward E, Berlinguer-Palmini Rolando R, Owens Andrew A, Greaves Laura C LC, Kolsky Kathy L KL, Parini Angelo A, Douin-Echinard Victorine V, LeBrasseur Nathan K NK, Arthur Helen M HM, Tual-Chalot Simon S, Schafer Marissa J MJ, Roos Carolyn M CM, Miller Jordan D JD, Robertson Neil N, Mann Jelena J, Adams Peter D PD, Tchkonia Tamara T, Kirkland James L JL, Mialet-Perez Jeanne J, Richardson Gavin D GD, Passos João F JF"],"additional_accession":[]},"is_claimable":false,"name":"Cardiomyocyte Telomere Damage by ROS without Cell Division","description":"No description","dates":{"last_modification":"2019-02-14","publication":"2019-02-14","submission":"2016-08-25"},"accession":"MODEL1608250001","cross_references":{"pubmed":["30737259"],"biomodels__db":["MODEL1608250001"]}}