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-κ B 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-κ B, 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 cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short-and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)