Invited Applicant Summaries for the MRC National Mouse Genetics Network – Full cluster proposals 2021 Call . 1

clinical need to understand and treat age-related multimorbidity Age-related multimorbidity (two or more chronic diseases) is responsible for over 50% of GP consultations and expected to rise. Currently, each disease is treated individually leading to polypharmacy, increased adverse effects, and reduced efficacy. New cost-effective ways to prevent multimorbidity are required to ensure sustainable healthcare costs. Clinical evidence suggests that the presence of one disease accelerates the onset of others with ageing being a key risk factor. The EU consortium MouseAGE has identified that a lack of animal models of multimorbidity in the context of an ageing physiology and the tendency to study each disease in isolation are barriers to developing new interventions. At present, mouse models reproduce characteristics of single diseases and largely involve young mice. This does not allow for the study of the interaction between diseases and/or drugs and the impact of ageing on their development and trajectories. We propose the formation of an interdisciplinary group to make use of artificial intelligence and patient data to drive the development and full characterization of complex age-appropriate models of multimorbidity. These models will improve the understanding of the commonality of biological mechanisms between diseases and will act as more reliable tools to test new cost-effective interventions. Lead: Professor Ilaria Bellantuono Professor in Musculoskeletal Ageing Co-Director of The Healthy Lifespan Institute (HELSI) Healthy Lifespan Institute & MRC Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA) Department of Oncology and Metabolism The School of Medicine. The University of Sheffield