The nuclear hormone receptor, 'liver X receptor beta', in skin ageing

Abstract

This thesis, "The Nuclear Hormone Receptor, Liver X Receptor β, In Skin Ageing" issubmitted to The University of Manchester by Christopher Thomas Ford for thedegree of Doctor of Philosophy (PhD) in the year of 2010.The nuclear hormone receptor (NHR) liver X receptor β (LXRβ) has been highlightedas a possible candidate for involvement in ageing by several recent findings. LXRβ isthe closest human homologue to the longevity-associated gene daf-12 in thenematode worm and LXRalpha haplotypes have been associated with longevity at oldages in a longitudinal human genetic study. Whilst LXRalpha is primarily responsible formediating the effects of LXR oxysterol ligands throughout most of the body, LXRβ isthe primary mediator of these effects uniquely in the skin. In this thesis studies arepresented on the expression of LXRβ mRNA and protein in human skin, comparingyoung vs intrinsically (chronologically) aged skin, photoprotected vs photoaged (dueto ultraviolet radiation exposure) skin and untreated vs retinoid-treated photoagedskin, retinoid treatment being a primary clinical intervention for photoageing. In situhybridisation and quantitative polymerase chain reaction (qPCR) were used toidentify LXRβ mRNA and immunofluorescence was used to identify LXRβ protein.These comparisons revealed that both the mRNA and protein expression of LXRβare highly stable throughout the ageing, photoageing and retinoid treatment ofhuman skin. Previous authors have identified overlap between microarray geneexpression datasets in the LXRβ-/- mouse and in normal human skin ageing. In thesestudies comparisons of different microarray datasets have been conducted with thefinding that LXR agonist treatment of mice produces gene regulation patterns withsignificant overlap to that seen in both ageing and calorie restriction in mice(binomial test; p

Date of Award	1 Aug 2011
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Rachel Watson (Supervisor) & Christopher Griffiths (Supervisor)