A mechanistic study of anti-ageing interventions in translation

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Ageing is known to be a malleable process, with interventions in a range of cellular processes leading to extended lifespans and healthspans. Translation is one such process in which improved translational fidelity at the stage of decoding has been shown to extend lifespans, and conversely reduced fidelity has been shown to decrease lifespans. Many factors have been shown to modulate this fidelity including the slowing of translation elongation, the inhibition of translation factors, and the introduction of point mutations into RPS23; a ribosomal protein. Despite these observations, the specific mechanisms by which these alterations improve translational fidelity and thus lifespans have not been determined. During this project, biochemical assays such as dual luciferase reporter assays, and structural biology techniques including cryo-electron microscopy and mass spectrometry will be used to ascertain precisely how these interventions alter the translational machinery. With this mechanistic and structural knowledge base it may then be possible to investigate and design small molecule drugs and inhibitors that can recapitulate these life extending effects providing a viable means for improving lifespans and potentially more importantly, an individual's healthy life expectancy.