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C. elegans ageing - Dr Jon Houseley


The discovery of mutations that can profoundly extend organismal lifespan has revealed that longevity is not absolutely limited by cells 'wearing out', but is partly genetically predetermined. Ageing is actually influenced by a complex mixture of genetic and environmental factors, and an unexpected epigenetic component was recently described in C. elegans. Worms carrying mutations in the histone modifying complex COMPASS live longer, but so do their wildtype children, grandchildren and great-grandchildren, showing that a heritable epigenetic change occurs in COMPASS mutants. However, the nature of this change is completely unknown.    Most characterised mutations and treatments that extend lifespan target energy metabolism. In yeast, lifespan mutants affect mechanisms controlling ribosome synthesis; this makes sense as ribosomes are energetically expensive to produce and operate, and their numbers are tailored to cellular requirements. The genes for ribosomal RNA are the most highly expressed in any cell and exist in multiple copies. In fact, ribosomal RNA genes occur in a tandem array called the ribosomal DNA (rDNA) whose copy number is tightly regulated by controlled recombination. Mutations that specifically decrease rDNA recombination enhance lifespan, and vice versa.    We have found that yeast COMPASS mutants have defects in rDNA recombination, leading to pronounced changes in rDNA structure, and we suspect that the observed epigenetic lifespan extension in C. elegans COMPASS mutants may stem from these rDNA changes. The aim of this project is to assess the heritability of rDNA changes in budding yeast COMPASS mutants and to assess their effects on lifespan.