Abstract

Age-related multimorbidity is a common feature of old age and can result in decreased life expectancy. Clinical management is typically accompanied by polypharmacy and expense in a healthcare system focused on treating individual diseases. Targeting the core processes that drive ageing offers a new approach for treating multimorbidity and has been demonstrated in preclinical models and in clinical trials with repurposed drugs. Here I will describe some of the work undertaken by the UK SPINE project, a collaboration between the Universities of Oxford, Birmingham and Dundee, The Francis Crick Institute, EMBL-EBI and MDC, focused on age-related drug discovery for multimorbidity. These efforts focused on key pathways and mechanisms central to the process of ageing and which interact to drive many features of multimorbidity. We identified and triaged targets associated with these pathways and with the potential to modulate age-related phenotypes and morbidities. Targets were screened using bespoke virtual, biochemical, biophysical and/or cellular based assays, alongside development of translational molecular biomarkers. This has allowed us to identify a new molecules and biomarker signatures that can be used to further probe the biology of ageing and multimorbidity and which have the potential to be further developed as drug project starting points.