Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorMartinez Guimera, Alvaro-
dc.descriptionPhD Thesisen_US
dc.description.abstractAgeing and disease can be understood in terms of a loss in biological homeostasis. This will often manifest as a constitutive elevation in the basal levels of biological entities. Examples include chronic inflammation, hormonal imbalances and oxidative stress. 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 a computational modelling approach is undertaken to examine how chronic oxidative stress can interfere with signal processing by redox signalling pathways in the cell. A primary outcome of this study is that constitutive signals can give rise to a ‘molecular habituation’ effect that can prime for a gradual loss of biological function. Experimental results obtained highlight the difficulties in testing for this effect in cell lines exposed to oxidative stress. However, further analysis suggests this phenomenon is likely to occur in different signalling pathways exposed to persistent signals and potentially at different levels of biological organisation.en_US
dc.description.sponsorshipCentre for Integrated Research into Musculoskeletal Ageing (CIMA) and through them, Arthritis Research UK and the Medical Research Councien_US
dc.publisherNewcastle Universityen_US
dc.titleInvestigating homeostatic disruption by constitutive signals during biological ageingen_US
Appears in Collections:Institute for Cell and Molecular Biosciences

Files in This Item:
File Description SizeFormat 
Martinez Guimera, A. 2018.pdfThesis9.51 MBAdobe PDFView/Open
dspacelicence.pdfLicence43.82 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.