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‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age
The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals impl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science Ireland
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846846/ https://www.ncbi.nlm.nih.gov/pubmed/29146308 http://dx.doi.org/10.1016/j.mad.2017.11.010 |
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author | Martinez Guimera, Alvaro Welsh, Ciaran M. Proctor, Carole J. McArdle, Anne Shanley, Daryl P. |
author_facet | Martinez Guimera, Alvaro Welsh, Ciaran M. Proctor, Carole J. McArdle, Anne Shanley, Daryl P. |
author_sort | Martinez Guimera, Alvaro |
collection | PubMed |
description | The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained oxidative stress. This is a perspective of studying oxidative stress as a constitutive signal within the cell. In this work, we adopt a theoretical perspective as an exploratory and explanatory approach to examine how chronic oxidative stress can interfere with signal processing by redox signalling pathways in the cell. We report that constitutive signals can give rise to a ‘molecular habituation’ effect that can prime for a gradual loss of biological function. This is because a constitutive signal in the environment has the potential to reduce the responsiveness of a signalling pathway through the prolonged activation of negative regulators. Additionally, we demonstrate how this phenomenon is likely to occur in different signalling pathways exposed to persistent signals and furthermore at different levels of biological organisation. |
format | Online Article Text |
id | pubmed-5846846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier Science Ireland |
record_format | MEDLINE/PubMed |
spelling | pubmed-58468462018-03-13 ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age Martinez Guimera, Alvaro Welsh, Ciaran M. Proctor, Carole J. McArdle, Anne Shanley, Daryl P. Mech Ageing Dev Article The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained oxidative stress. This is a perspective of studying oxidative stress as a constitutive signal within the cell. In this work, we adopt a theoretical perspective as an exploratory and explanatory approach to examine how chronic oxidative stress can interfere with signal processing by redox signalling pathways in the cell. We report that constitutive signals can give rise to a ‘molecular habituation’ effect that can prime for a gradual loss of biological function. This is because a constitutive signal in the environment has the potential to reduce the responsiveness of a signalling pathway through the prolonged activation of negative regulators. Additionally, we demonstrate how this phenomenon is likely to occur in different signalling pathways exposed to persistent signals and furthermore at different levels of biological organisation. Elsevier Science Ireland 2018-01 /pmc/articles/PMC5846846/ /pubmed/29146308 http://dx.doi.org/10.1016/j.mad.2017.11.010 Text en © 2017 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Martinez Guimera, Alvaro Welsh, Ciaran M. Proctor, Carole J. McArdle, Anne Shanley, Daryl P. ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title | ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title_full | ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title_fullStr | ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title_full_unstemmed | ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title_short | ‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
title_sort | ‘molecular habituation’ as a potential mechanism of gradual homeostatic loss with age |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846846/ https://www.ncbi.nlm.nih.gov/pubmed/29146308 http://dx.doi.org/10.1016/j.mad.2017.11.010 |
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