Rogan, Abbie JT;
(2022)
RNA polymerase I and III and their roles in lifespan and healthspan of Drosophila Melanogaster.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The reduction of activity of RNA polymerase I and III (Pol I and III) extends lifespan and these effects can be mediated by one organ; the gut. This thesis explores how reduced activity of Pol I or III in Drosophila impacts health. I explored the effect of reduced Pol I or Pol III activity on neuromuscular health through observing changes in climbing behaviour. Reduced activity of Pol I in the gut, and in particular, the intestinal stem cells, mediates the amelioration of neuromuscular decline through non-cell autonomous effects. Furthermore, I investigated the impact of reduced Pol I or III activity on quantity and quality of sleep and activity through Drosophila activity monitoring assays. Pol III mutants are hyperactive relative to controls and protect against age-related increase in sleep fragmentation. Pol I mutants are hyperactive during the day and ameliorate age-related decline in day activity; the former phenotype is recapitulated by enterocyte specific knockdown of Pol I. Pol I mutants also protect against age-related increase in total sleep which again is recapitulated by gut specific knockdown of Pol I. Additionally, I conducted an exploratory investigation of gene expression changes in Drosophila with reduced Pol III activity in the gut with the aim of elucidating how the gut can alter wider organismal health. This analysis identified genes encoding secreted proteins including neuroendocrine peptides, as well as genes involved in lipid metabolism, autophagy and immune signalling that were differentially regulated in this intervention. Finally, I analysed nucleolar size in guts of Pol I and Pol III mutants. Pol I mutants have reduced nucleolar size relative to controls whilst Pol III mutants’ nucleoli are not significantly altered. The reduced activity of Pol I or Pol III can improve indices of health in older flies. These effects are not the same between the Pols or on different aspects of health and some may be mediated by non-cell autonomous mechanisms.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | RNA polymerase I and III and their roles in lifespan and healthspan of Drosophila Melanogaster |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | 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 UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158392 |
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