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Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk
Autophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to ageing. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the ageing process, and whether au...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965206/ https://www.ncbi.nlm.nih.gov/pubmed/31949142 http://dx.doi.org/10.1038/s41467-019-14187-x |
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author | Cassidy, Liam D. Young, Andrew R. J. Young, Christopher N. J. Soilleux, Elizabeth J. Fielder, Edward Weigand, Bettina M. Lagnado, Anthony Brais, Rebecca Ktistakis, Nicholas T. Wiggins, Kimberley A. Pyrillou, Katerina Clarke, Murray C. H. Jurk, Diana Passos, Joao F. Narita, Masashi |
author_facet | Cassidy, Liam D. Young, Andrew R. J. Young, Christopher N. J. Soilleux, Elizabeth J. Fielder, Edward Weigand, Bettina M. Lagnado, Anthony Brais, Rebecca Ktistakis, Nicholas T. Wiggins, Kimberley A. Pyrillou, Katerina Clarke, Murray C. H. Jurk, Diana Passos, Joao F. Narita, Masashi |
author_sort | Cassidy, Liam D. |
collection | PubMed |
description | Autophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to ageing. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the ageing process, and whether autophagy restoration can counteract these ageing effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan; however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumour formation. Thus, our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumour suppressive and oncogenic, sequentially. |
format | Online Article Text |
id | pubmed-6965206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69652062020-01-22 Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk Cassidy, Liam D. Young, Andrew R. J. Young, Christopher N. J. Soilleux, Elizabeth J. Fielder, Edward Weigand, Bettina M. Lagnado, Anthony Brais, Rebecca Ktistakis, Nicholas T. Wiggins, Kimberley A. Pyrillou, Katerina Clarke, Murray C. H. Jurk, Diana Passos, Joao F. Narita, Masashi Nat Commun Article Autophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to ageing. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the ageing process, and whether autophagy restoration can counteract these ageing effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan; however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumour formation. Thus, our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumour suppressive and oncogenic, sequentially. Nature Publishing Group UK 2020-01-16 /pmc/articles/PMC6965206/ /pubmed/31949142 http://dx.doi.org/10.1038/s41467-019-14187-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Cassidy, Liam D. Young, Andrew R. J. Young, Christopher N. J. Soilleux, Elizabeth J. Fielder, Edward Weigand, Bettina M. Lagnado, Anthony Brais, Rebecca Ktistakis, Nicholas T. Wiggins, Kimberley A. Pyrillou, Katerina Clarke, Murray C. H. Jurk, Diana Passos, Joao F. Narita, Masashi Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title | Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title_full | Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title_fullStr | Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title_full_unstemmed | Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title_short | Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
title_sort | temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965206/ https://www.ncbi.nlm.nih.gov/pubmed/31949142 http://dx.doi.org/10.1038/s41467-019-14187-x |
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