@article{848508acb2fd460c8f6d9b5fedc362a1,
title = "Chronic inflammation induces telomere dysfunction and accelerates ageing in mice",
abstract = "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.",
author = "Diana Jurk and Caroline Wilson and Passos, {Jo{\~a}o F.} and Fiona Oakley and Clara Correia-Melo and Laura Greaves and Gabriele Saretzki and Chris Fox and Conor Lawless and Rhys Anderson and Graeme Hewitt and Pender, {Sylvia L.F.} and Nicola Fullard and Glyn Nelson and Jelena Mann and {Van De Sluis}, Bart and Mann, {Derek A.} and {Von Zglinicki}, Thomas",
note = "Funding Information: The study was supported by BBSRC (grants BB/C008200/1 and BB/I020748/1 to T.v.Z.), the UK Medical Research Council (MICA Programme Grant MK/K001949/1 to D.A.M., grants G0700890 to D.A.M. and F.O. and G0900535 to F.O.), the Wellcome Trust (grant WT084961MA to D.A.M.), a European Commission FP7 programme grant {\textquoteleft}INFLA-CARE{\textquoteright} (EC Contract No. 223151; http://inflacare.imbb.forth.gr/) and grants from the Newcastle Biomedical Research Centre (T.v.Z. and D.A.M.) and the National Institute for Health Research (D.A.M.). We thank Neil Perkins, Patrick Chinnery, Chris Day and Tom Kirkwood for critical discussion of the manuscript.",
year = "2014",
month = jun,
day = "24",
doi = "10.1038/ncomms5172",
language = "English",
volume = "2",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}