Skip to Main content Skip to Navigation

Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02445949
Contributor : Jeanne Mialet-Perez <>
Submitted on : Monday, January 20, 2020 - 3:02:47 PM
Last modification on : Friday, January 24, 2020 - 1:02:40 AM

Identifiers

Collections

Citation

Rhys Anderson, Anthony Lagnado, Damien Maggiorani, Anna Walaszczyk, Emily Dookun, et al.. Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence. EMBO Journal, EMBO Press, 2019, 38 (5), pp.e100492. ⟨10.15252/embj.2018100492⟩. ⟨inserm-02445949⟩

Share

Metrics

Record views

23

Files downloads

58