The cell biology of senescence is reviewed, with particular emphasis on models and theories derived from work with cultured human -fibrbblas: ts. The. biochemistry-and. cell biology of Werner's Syndrome is reviewed, and- the relationship of this genetic disease-to the natural ageing process is. examined... Similarities and'differenc. es between Werner s Syndrome fibroblast cultures . 'arid: those derived " from normal individuals are given special attention. The work presented in this thesis was undertaken to determine whether cells derived from patients suffering from Werner's Syndrome behaved differently in culture to those derived from normal donors. Such a phenotype could be used in the long term to assist current attempts to clone the Werner'-s Syndrome gene. The cell kinetic aspects of -the -Syndrome were studied' because an important feature of the disease is that fibroblasts derived from Werner's Syndrome patients are known to grow extremely poorly in vitro. The data presented show that Werner's Syndrome fibroblasts exhibit a severely restricted in vitro lifespan due to a three to five fold increase in the rate at which the cells exit irreversibly from the cell cycle and become senescent. It is also shown that this behaviour is not due to abnormalities in hyaluronic acid metabolism in vitro despite the fact that elevated levels of hyaluronic acid are diagnostic for Werner's Syndrome patients. Finally, it is demonstrated that cultures of Werner's Syndrome T lymphocytes do not show a reduced li fespan which is highly suggestive that the condition is restricted to a subset of cellular lineages. The effect of these findings on theoretical models of cellular senescence is discussed, as is the practical impact of this data on the ongoing attempt to characterise the Werner's Syndrome gene.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:357390 |
| Date | January 1993 |
| Creators | Faragher, Richard G. A. |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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