Toggle Main Menu Toggle Search

Open Access padlockePrints

Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

Lookup NU author(s): Dr Diana Jurk, Dr Caroline Wilson, Dr Joao Passos, Professor Fiona Oakley, Clara Correia Melo, Dr Laura Greaves, Dr Gabriele Saretzki, Christopher Fox, Dr Conor Lawless, Rhys Anderson, Dr Graeme Hewitt, Nicola Fullard, Dr Glyn Nelson, Professor Jelena Mann, Professor Derek Mann, Professor Thomas von Zglinicki

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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-kB 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-kB, 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


Publication metadata

Author(s): Jurk D, Wilson C, Passos J, Oakley F, Correia-Melo C, Greaves L, Saretzki G, Fox C, Lawless C, Anderson R, Hewitt G, Pender SLF, Fullard N, Nelson G, Mann J, van de Sluis B, Mann DA, von Zglinicki T

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2014

Volume: 2

Print publication date: 24/06/2014

Online publication date: 24/06/2014

Acceptance date: 20/05/2014

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms5172

DOI: 10.1038/ncomms5172


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share