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Chronic inflammation induces telomere dysfunction and accelerates ageing in mice
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090717/ https://www.ncbi.nlm.nih.gov/pubmed/24960204 http://dx.doi.org/10.1038/ncomms5172 |
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author | 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 |
author_facet | 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 |
author_sort | Jurk, Diana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4090717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40907172014-07-11 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 Nat Commun Article 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. Nature Pub. Group 2014-06-24 /pmc/articles/PMC4090717/ /pubmed/24960204 http://dx.doi.org/10.1038/ncomms5172 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-by/3.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article 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 Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title | Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title_full | Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title_fullStr | Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title_full_unstemmed | Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title_short | Chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
title_sort | chronic inflammation induces telomere dysfunction and accelerates ageing in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090717/ https://www.ncbi.nlm.nih.gov/pubmed/24960204 http://dx.doi.org/10.1038/ncomms5172 |
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