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Title: Investigating the role of lysine demethylase UTX-1 in lifespan regulation of C. elegans
Author: Guillermo, Abigail
ISNI:       0000 0004 7654 3634
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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That ageing can be epigenetically regulated has garnered considerable interest due to the implication that ageing is incredibly plastic and therefore, potentially reversible. Overexpression and downregulation of utx-1 (H3K27me2/3-specific lysine demethylase UTX-1) was found to promote lifespan extension in C. elegans. Because utx-1 is ubiquitously expressed, it was hypothesised that lifespan is differentially affected, depending on the tissue where utx-1 expression is manipulated. Hypodermis-, intestineand neuron-specific knockdown of utx-1 (but not muscle) was found to promote lifespan extension in worms, whereas, overexpression of utx-1 only in intestine and neurons (but not muscle and hypodermis) promoted longevity. The catalytic activity of UTX-1 was found to be necessary for lifespan extension due to utx-1 overexpression and RNA-Seq studies showed that utx-1 overexpression is associated with upregulation of defense and immune response genes - a possible protective mechanism that indirectly promotes lifespan extension in worms. Finally, hsp-1 (heat-shock protein hsp-70) was discovered to be absolutely required for lifespan extension due to utx-1 overexpression, suggesting that the heat-shock response is crucial for lifespan regulation mediated by utx-1 overexpression. Overall, the work in this thesis, which also includes analysis of cbp-1 (H3K27 acetyl transferase), suggests that lifespan regulation due to H3K27 modification is incredibly complex and that longevity is mediated differentially as a consequence of different doses of modifier, and in specific tissues, likely due to transcriptional changes mediated by the demethylase function of UTX-1.
Supervisor: Woollard, Alison Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Aging