Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut. nfkb1(-/-) fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-κB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in nfkb1(-/-) tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent…

• WT
  Wellcome Trust

  Award: G0900535
• NI
  National Institute for Health and Care Research
• EC
  European Commission

  Award: 223151
• MR
  Medical Research Council

  Awards: G0900535, MR/L016354/1, MK/K001949/1, G0700890, MR/K001949/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/C008200/1, BB/K017314/1, BB/I020748/1, BB/F010966/1, BB/I020748/1, BB/H022384/1
• NN
  NIHR Newcastle Biomedical Research Centre