Doctoral Degrees (Physiological Sciences)

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Browsing Doctoral Degrees (Physiological Sciences) by Subject "Age factors in disease"

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    Chronic stress-associated accelerated ageing: inflammation and oxidative stress treatment
    (Stellenbosch : Stellenbosch University, 2020-12) Petersen-Ross, Kelly Shirley; Smith, Carine; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: In recent years, the incidence of non-communicable diseases (NCD) normally associated with advanced age has begun presenting in younger populations. This has resulted in a growing burden on global healthcare systems and decreasing quality of life in individuals. Cardiovascular diseases, cancers, chronic respiratory diseases, chronic inflammatory diseases and diabetes are some of the many NCD’s and all these have two maladaptive characteristics in common, namely chronic low-grade inflammation and increased oxidative stress. The aim of this research was to identify a threshold prior to maladaptation in both redox and inflammatory status which can be targeted with preventative medicine strategies; in this way, we may identify suitable models which are sensitive enough to identify this threshold as well as show small effect sizes so that they can be used for drug screening of preventative medicine treatments. In order to elucidate this threshold, two rodent models were employed to simulate a pre-onset and an early onset state. The pre-onset state was simulated by chronic D-galactose injections to mimic cumulative oxidative stress as is associated with chronological ageing. The early onset state was simulated with a collagen induced rheumatoid arthritis (RA) model. A grape seed polyphenol supplementation was employed to assess the sensitivity of the models. Comprehensive end-point analysis of the oxidative and inflammatory state of various compartments were performed. Analysis of parameters associated with ageing were also included as measure of relative ageing status in models. The results of both studies indicated that the threshold or point of onset of accelerated ageing was indeed identified. In the D-galactose model, a novel finding was the compromised antioxidant capacity in plasma, even in the absence of experimentally elevated oxidative damage, observed as decreases in plasma FRAP. However, oxidative damage was observed in tissue specific investigations, such a morphological changes in the mesenteric lymph nodes. In the RA model, decreases in antioxidant capacity was noted along with oxidative damage in plasma, but not in all tissue types investigated - particularly the brain. This novel finding of pre-damage oxidative changes in the brain was indicated by decreases in MDA and increases in FRAP. This combined with a switch to a pro-inflammatory state within the circulation, confirms the early disease state within the RA model. This investigation has elucidated the importance of monitoring the oxidative state within multiple compartments to identify the threshold at which disturbances to homeostasis turns into maladaptation and FRAP may be the most sensitive parameter to display this. The effect changes noted after supplementation with an antioxidant treatment also enhanced our knowledge of which parameters and tissue are susceptible to oxidative and inflammatory modulation to prevent maladaptations which may result in pathology.