Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence

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…

• FF
  Foundation for the National Institutes of Health

  Award: AG013925
• NF
  Noaber Foundation
• BH
  British Heart Foundation

  Award: PG/15/85/31744
• RO
  Région Occitanie Pyrénées-Méditerranée
• NI
  National Institutes of Health

  Award: AG013925
• MR
  Medical Research Council

  Award: MR/L016354/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/K017314/1, BB/K017314/1, BB/H022384/1, BB/H022384/1