Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence
Résumé
Ageing is the biggest risk factor for cardiovascular health and is associated with increased incidence of 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 if 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. Pharmacological or genetic clearance of senescent cells in mice alleviates myocardial hypertrophy and fibrosis, detrimental features 2 of cardiac ageing, and promotes cardiomyocyte regeneration. Our data describes a mechanism by which senescence can occur and contribute to ageing in post-mitotic tissues.
Fichier principal
Anderson_et_al-2019-The_EMBO_Journal.pdf (2.11 Mo)
Télécharger le fichier
Anderson et al. 2018.pdf (6.16 Mo)
Télécharger le fichier
Origine | Publication financée par une institution |
---|
Origine | Fichiers produits par l'(les) auteur(s) |
---|
Loading...