Exploring the Effects of Ageing on the Host-Microbiota Axis Skin Repair

Abstract

Abstract Anna Bornikoel University of Manchester Doctor of Philosophy April 2019 The prevalence of perturbed wound healing, characterised by dysregulated inflammation and often accompanied by bacterial infections, is increased with progressing age. Age-related changes in the skin microbiota or the response to bacterial products may contribute to the dysregulated inflammatory and perturbed wound healing response. This was explored by examining the expression and function of pattern recognition receptors (PRRs), which initiate inflammation in response to bacterial product exposure, in vitro and in vivo as well as their potential impact on the wound healing response with increased age. In vitro PRR stimulation of neutrophils and macrophages from wounded mice demonstrated age-related differences in PRR and downstream cytokine expression (TNF, IL-β, IL-6 and IL-12) with increased age. Although 5-7 week and 18 month old mice showed similar responses to PRR ligand stimulation, 22-24 month old mice showed an impaired response. Examination of PRR expression and function with increasing age further highlighted the importance of considering the temporal aspect of the response to PRR ligand treatment, as changes in PRR expression and function with increased age differed considerably in response to 3h compared to 24h treatment. Interestingly, TLR1, TLR2 and TLR4 mRNA expression was significantly increased in untreated wounds of aged (22-24 month old) compared to young (5-7 weeks) mice, while the wound healing response to PRR ligand treatment in aged was impaired. Thus, the results presented here demonstrate age-related changes in response to PRR ligand exposure, which may contribute to the dysregulated inflammatory response associated with impaired wound healing in the aged, as well as potentially delaying other aspects of wound healing.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Kimberly Mace (Supervisor)