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'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age

Lookup NU author(s): Alvaro Martinez Guimera, Ciaran Welsh, Dr Carole Proctor, Dr Daryl Shanley



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


© 2017. 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.

Publication metadata

Author(s): Martinez Guimera A, Welsh CM, Proctor CJ, McArdle A, Shanley DP

Publication type: Article

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2018

Volume: 169

Pages: 53-62

Print publication date: 01/01/2018

Online publication date: 14/11/2017

Acceptance date: 10/11/2017

Date deposited: 23/02/2018

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier Ireland Ltd


DOI: 10.1016/j.mad.2017.11.010


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Funder referenceFunder name
Arthritis Research UK
MR/K006312/1Medical Research Council (MRC)
MR/K006312/1Medical Research Council (MRC)