How does run-on of developmental processes contribute to ageing? (360G-Wellcome-301529_Z_23_Z)

This project aims to enable therapies for healthy ageing by using our established Drosophila discovery platform for genes that coordinate development while also having detrimental effects in later life. Age- associated multimorbidity is the costliest health challenge to the wellbeing of the global ageing population, thus we need therapies aimed at the biology of ageing. To enable focused therapy development, we need to identify the tissues and molecular mechanisms by which known signalling pathways modulate healthy ageing across animals, and to discover additional pathways for new therapeutic repertoires. This project will combine Drosophila genetics with assays of longevity and functional decline to address these needs. In Aim 1, we will genetically inhibit receptor tyrosine kinases (RTKs) with distinct tissue expression patterns to identify key tissues modulating healthy ageing. In Aim 2, we will characterise age-related protein aggregation and autophagy as a potential anti-ageing mechanism downstream of RTK inhibition. In Aim 3, we will genetically inhibit non-RTK signalling pathways with evolutionarily conserved roles in development to identify additional signalling pathways that can modulate healthy ageing. Ultimately, we will disseminate our findings to researchers working in mammalian models as the next stage of the pipeline towards therapies aimed at the biology of ageing.