Diana Jurk
Chronic inflammation induces telomere dysfunction and accelerates ageing in mice
Jurk, Diana; Wilson, Caroline; Passos, João F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia LF; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas
Authors
Caroline Wilson
João F. Passos
Fiona Oakley
Clara Correia-Melo
Laura Greaves
Gabriele Saretzki
Chris Fox
Conor Lawless
Rhys Anderson
Graeme Hewitt
Sylvia LF Pender
Dr Nicola Fullard nicola.fullard@durham.ac.uk
Chief Experimental Officer
Glyn Nelson
Jelena Mann
Bart van de Sluis
Derek A. Mann
Thomas von Zglinicki
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-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 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.
Citation
Jurk, D., Wilson, C., Passos, J. F., Oakley, F., Correia-Melo, C., Greaves, L., Saretzki, G., Fox, C., Lawless, C., Anderson, R., Hewitt, G., Pender, S. L., Fullard, N., Nelson, G., Mann, J., van de Sluis, B., Mann, D. A., & von Zglinicki, T. (2014). Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nature Communications, 5(1), https://doi.org/10.1038/ncomms5172
Journal Article Type | Article |
---|---|
Acceptance Date | May 20, 2014 |
Online Publication Date | Jun 24, 2014 |
Publication Date | Jun 24, 2014 |
Deposit Date | Aug 9, 2021 |
Journal | Nature Communications |
Electronic ISSN | 2041-1723 |
Publisher | Nature Research |
Peer Reviewed | Peer Reviewed |
Volume | 5 |
Issue | 1 |
DOI | https://doi.org/10.1038/ncomms5172 |
Public URL | https://durham-repository.worktribe.com/output/1268706 |
You might also like
Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age
(2024)
Journal Article
Bioengineering the Microanatomy of Human Skin
(2019)
Journal Article
PyCoTools: a Python toolbox for COPASI
(2018)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search