LAHAT, ALBERT (2019) TRANSCRIPTOMIC STUDIES IN AGEING AND SENESCENCE. Doctoral thesis, Durham University.
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Author-imposed embargo until 04 June 2022.
Senescence is known as an irreversible departure from the cell cycle and is considered a leading factor in the ageing phenotype, including age related diseases. With limited exception (such as negligible senescence and biologically immortal organisms), all cells reach a senescent state and all organisms age.
The advent of Next-Generation Sequencing (NGS) technology has enabled the study of the cellular transcriptome in a highly intimate manner. From NGS experiments it is possible to infer both the quantity and isoform of a transcript of interest. Currently, an ever-growing body of easily accessible NGS experimental data has allowed researchers to foster collaborative endeavours by utilizing datasets from diverse experiments to ask new questions. Here, we study datasets from mouse tissue samples across the lifespan under a normal ad libitum diet or under 40% dietary restriction, and human cell lines which have undergone replicative senescence or irradiation induced senescence. The overall aim of this study was to investigate ageing from a transcriptomic point of view.
Here, we focus on a series of parallel projects to study the landscape of changes occurring in ageing and senescence. We investigate differential gene expression, differential exon usage, and differential lncRNA expression. To further understand the biological relevance of the landscape changes, we utilized gene ontology (GO and Reactome) enrichment for differential expression changes, and we present a novel tool (MAltESERS) to understand the biological significance of alternative exon usage.
We found that there was post senescence plasticity, meaning that both expression and splicing were altered after senescence induction. Our data suggests that senescence in mouse hepatic tissue was induced suddenly and catastrophically. We also observed three systems (immune/inflammation, chromatin structure, and energy metabolism) being strongly altered and each system can strongly induce changes in the other, which may strengthen the irreversibility of senescence.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||Aeging; Senescence; Splicing; transcriptomics; Dietary Restriction|
|Faculty and Department:||Faculty of Arts and Humanities > East Asian Studies, Department of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||06 Jun 2019 12:40|