This thesis addresses two topics relating to the biology of ageing in C. elegans. The first is dietary restriction (DR), a treatment that is known increase longevity over a broad evolutionary range, from Protozoa to rodents. The mechanism by which DR works remains obscure, but it has been proposed that DR extends lifespan by lowering insulin/IGF-like (IIF) signalling, or by diverting resources from fertility into somatic maintenance. To test these possibilities requires quantitative application of DR. The first aim of this work was to establish such a DR method in C. elegans. To this end four reported methods were tested: Use of feeding defective mutants, use of agar plates with thinner bacterial lawns, use of bacterial dilution in liquid culture, and use of defined liquid medium. In all four cases, methodological shortcomings were identified. Thus, a good quantitative method of DR for C. elegans remains to be discovered. The second topic of this thesis is the oxidative damage theory of ageing. Despite being the focus of intense investigation, it remains unclear whether or not this theory is true. A range of antioxidants was applied in the expectation that they should retard ageing. In no case was this seen, even in the case of the SOD mimetics EUK-8 and EUK-134, previously reported to increase lifespan dramatically. Further studies were conducted to establish why SOD mimetics do not extend lifespan. Protection by SOD mimetics against pro-oxidants, in wild-type and hormesis-defective mutants implies that if superoxide levels limited lifespan as the oxidative damage theory predicts, then EUK-8 should increase lifespan. In fact even a EUK-8 dose optimised for protection against superoxide generators did not increase lifespan. The results in this thesis imply that oxidative damage due to superoxide is not the cause of ageing.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:682454 |
| Date | January 2004 |
| Creators | Keaney, M. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1446779/ |
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