Mitochondria are required for pro‐ageing features of the senescent phenotype

Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development of the senescent phenotype, which involves an overproduction of pro-inflammatory and pro-oxidant signals. However, the exact mechanisms regulating these phenotypes remain poorly understood. Here, we show the critical role of mitochondria in cellular senescence. In multiple models of senescence, absence of mitochondria reduced a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced glycolysis. Global transcriptomic analysis by RNA sequencing revealed that a vast number of senescent-associated changes are dependent on mitochondria, particularly…

• A
  AstraZeneca
• NU
  Newcastle University
• UD
  Universidade do Porto
• MR
  Medical Research Council

  Awards: MR/K006312/1, MR/L016354/1, MC_G0802535, MR/K001949/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/K019260/1, BB/K017314/1, BB/K017314/1, BB/K019260/1, BB/K017233/1, BB/I020748/1, BB/H022384/1, BB/M023389/1, BB/J007803/1, BB/F010966/1, BB/I020748/1, BB/H022384/1
• FP
  Fundação para a Ciência e a Tecnologia