The role of translational control in regulating chronological lifespan

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Trying to understand why do we age has been a long standing question. It is a complicated question because it is not only our genes, but the environment and diet that affects the way we age. In order to identify mechanisms underlying the ageing processes, simple model organisms have been studied. The budding yeast, Saccharomyces cerevisiae, provides one of the simplest and widely adopted model organisms to study ageing. It provides a relatively simple, genetically tractable system, and has provided a number of significant advances in our understanding of the ageing process in human cells. For example, it has been used to identify major pro-ageing pathways which are highly conserved in organisms ranging from yeast to humans. We are using this model and have found that a that a key protein synthesis factor is important for ensuring longevity. Protein synthesis factors are required to synthesize all new proteins in each cell, a process referred to as "translation". These 'protein synthesis factors' translate RNA, a messenger molecule that encodes gene sequences, into protein molecules. There are many thousands of RNA molecules in each cell, each one carrying instructions (or coding) for a different protein. The protein synthesis factors must interact with each RNA in the right way so that each new protein is made correctly and in the correct proportions. By improving our fundamental understanding of how such processes work in normal cells it can help scientists understand diseases in which this process is altered. Our preliminary data indicate that one such translation factor (eIF4G) is essential for longevity in our yeast model of ageing. This project will address how eIF4G regulates translation during ageing and whether there are specific eIF4G target RNAs that ensure a normal healthy ageing process.