Gilliat, AF;
(2017)
The study of senescent pathology in Caenorhabditis elegans.
Doctoral thesis , UCL (University College London).
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Abstract
The aim of this work is to identify the biological mechanisms of ageing, which remain poorly understood. One model organism widely used by biogerontologists is C. elegans. Here lifespan is, one assumes, a function of life limiting senescent pathologies. However, the cause of senescent pathologies and the identity of those pathologies that limit life are unclear. Therefore the main goals of my PhD were to understand where senescent pathologies come from and to identify the pathologies that limit worm lifespan. Using Nomarski microscopy, pathology within various tissues of the germline and soma was examined during ageing. The C. elegans intestine is the major somatic organ and is a likely location for lethal, senescent pathology. It undergoes major atrophy during ageing, which is demonstrated here to be driven by intestinal biomass conversion into yolk. To determine the pathology state at death, we performed necropsy analysis on the corpses of elderly worms. This revealed that the majority of early deaths occurred with an enlarged pharynx, reflecting severe bacterial infection. Combining survival and pathology data into a new pathology-centred approach has allowed new insights to be obtained into the determinants of late life disease and lifespan. It has long been widely believed that ageing was caused by molecular damage. However the recently proposed hyperfunction theory, which is related to the antagonistic pleiotropy theory, suggests that a major contributory cause of ageing is actually quasi-programmes. These are biological programmes essential for early-life fitness that continue to operate in a non-adaptive fashion in older organisms, such as intestinal biomass conversion to yolk. Thus hyperfunction may contribute to the development of age-related pathologies, some of which will cause death.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The study of senescent pathology in Caenorhabditis elegans |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Third party copyright material has been removed from ethesis. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1568036 |
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