Ageing is the primary risk factor for loss of function, frailty and ill health in older people. The proportion of individuals aged 65 or older is rapidly increasing, and identifying compounds that can prolong health-span is an urgent research priority. We have used computational approaches to identify candidate anti-ageing compounds. Our top-ranked hit, the HSP90 inhibitor tanespimycin, has proved to extend lifespan in both C. elegans and Drosophila. The project will use chemical-genetic screens, bioinformatics, and molecular biology to understand how HSP90 and, if time permits, a second chemical from the screen, promote healthy ageing in both worms and flies.
Fuentealba et al. Using the drug-protein interactome to identify anti-ageing compounds for humans. 2019. PLoS Comput. Biol.
Donertas et al. Gene expression-based drug repurposing to target aging. 2018. Aging Cell.
Donertas et al. Identifying potential ageing-modulating drugs in silico. 2019. Trends Endocrinol Metab.
Labbadia et al. Mitochondrial stress restores the heat shock response and prevents proteostasis collapse during ageing. 2017. Cell Rep.
Castillo-Quan et al. Lithium promotes longevity through GSK3/NRF2-dependent hormesis. 2016. Cell Rep