| First Author | Anderson R | Year | 2019 |
| Journal | EMBO J | Volume | 38 |
| Issue | 5 | PubMed ID | 30737259 |
| Mgi Jnum | J:277203 | Mgi Id | MGI:6323081 |
| Doi | 10.15252/embj.2018100492 | Citation | Anderson R, et al. (2019) Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J 38(5) |
| abstractText | 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(CIP) and p16(INK4a), 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. |
