Epigenetic Regulation of Ageing
Start date: Aug 1, 2012,
End date: Jul 31, 2016
Ageing is certainly one of the most interesting but less understood processes of multi-cellular organisms. Although in the last decade great advances have been made to understand the molecular mechanism of ageing a unifying model is still elusive. Research in C. elegans has focussed on the characterization of signalling pathways involved in ageing. It is was demonstrated that the gene expression of old nematodes differs significantly from young worms, however, the molecular mechanisms that govern the regulation of genes have not been addressed in the context of ageing. The central questions for the proposed project are therefore, which epigenetic marks govern the ageing of animals and how these marks are interpreted in the organism. Our epigenetic analysis in the course of ageing shows a significant impact of the histone H2A-ubiquitin mark in comparison with other epigenetic marks. This finding might be partially linked to the role of H2A-ubiquitin during DNA repair and to the dependence of H2A-ubiquitin levels on proteasome stability, which is altered during ageing. In another view H2A-ubiquitin and possibly other yet to defined epigenetic marks lead to the recruitment of epigenetic factors that drive ageing. The proposed research will identify the epigenetic enzymes that set and erase the H2A-ubiquitin mark and will prove them to be determinants of the life span of the worm. Furthermore, it will reveal how the H2A-ubiquitin mark is read in the course of ageing and reveal a protein complex that transmits the ageing signal further downstream. As a consequence the chromatin will most probably be decorated by other ageing relevant epigenetic marks, which will be identified as well in this study. The project should be of great importance not only to the scientific fields of epigenetics and ageing but should also have a great impact on applied sciences.
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