West, Melanie J.; (2004) The effect of oxidative stress on ageing in Drosophila melanogaster. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

For nearly five decades one of the most influential theories explaining the ageing process has been the free radical, or oxidative damage theory. Numerous studies have tested this theory in a range of organisms. Despite being the focus of intense investigation this theory remains unproven, and conflicting results abound. The primary aim of this thesis was therefore to critically test the oxidative damage theory using the fruitfly Drosophila melanogaster. If this theory is true, dietary administration of pharmacological agents that protect against or limit the production of oxygen radicals should retard ageing and increase lifespan. Here, three classes of such agents are investigated: non-catalytic antioxidants, catalytic antioxidants and protonophore uncouplers of mitochondrial oxidative phosphorylation. In most cases, no increase in lifespan was observed. Indeed the compounds tested largely showed dose-dependent toxicity. In addition, non- catalytic and catalytic antioxidants did not protect against increased oxidative stress. Taken all together, these results fail to support the oxidative damage theory of ageing. Ambient temperature affects the lifespan of poikilothermic organisms. It has been suggested that this is due to the effect of temperature on metabolic rate, with heightened production of ROS at higher temperature. If the oxidative damage theory is correct, this might explain why lifespan is shortened with increasing temperature in poikilotherms. To examine this, thiobarbituric acid reactive substances (TBARS) and malondialdehyde (MDA), both indicators of oxidative damage to lipids, and the endogenous antioxidant glutathione (GSH) were measured in flies maintained at two different temperatures. The results are inconclusive and require repeat trials before any conclusions can be definitively drawn.

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