| First Author | Jurk D | Year | 2014 |
| Journal | Nat Commun | Volume | 2 |
| Pages | 4172 | PubMed ID | 24960204 |
| Mgi Jnum | J:298722 | Mgi Id | MGI:6210518 |
| Doi | 10.1038/ncomms5172 | Citation | Jurk D, et al. (2014) Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat Commun 2:4172 |
| abstractText | 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-kappaB 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-kappaB, 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. |
