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Intrinsic muscle weakness (i.e., weakness without loss of muscle mass) is a comorbidity afflicting many patients including cancer, rheumatoid arthritis (RA) and cardiovascular disease, and our normal ageing population. Muscle weakness hinders a healthy lifestyle and is a leading cause of long-term sick leave. Despite the severe negative impact on the patients’ lives, there are currently no efficient clinical pharmacological therapeutic approaches to improve muscle strength, hence we urge a better understanding of this comorbidity. Here we will use a consolidating multi-disease approach (RA, breast cancer and peripheral artery disease) and cutting-edge technology to i) elucidate shared molecular signatures driving disease-induced muscle weakness and ii) apply a translational multi-disease exercise approach to identify novel targets to combat disease-induced muscle weakness. Human subjects and mouse models will undergo functional analyses in vivo and ex vivo, including muscle strength and cellular respirometry. Muscle will undergo additional detailed analyses, including live imaging, single cell profiling and bulk transcriptomics. The molecular signatures will be further elucidated by gain- and loss-of-function experiments in skeletal muscle and by novel in vivo models. The molecular insights will be groundbreaking for our understanding of disease-induced muscle weakness and used for determining future pathways of intervention to ultimately improve muscle function for patients.

Intrinsic muscle weakness (i.e., weakness without loss of muscle mass) is a comorbidity afflicting many patients including cancer, rheumatoid arthritis (RA) and cardiovascular disease, and our normal ageing population. Muscle weakness hinders a healthy lifestyle and is a leading cause of long-term sick leave. Despite the severe negative impact on the patients’ lives, there are currently no efficient clinical pharmacological therapeutic approaches to improve muscle strength, hence we urge a better understanding of this comorbidity. Here we will use a consolidating multi-disease approach (RA, breast cancer and peripheral artery disease) and cutting-edge technology to i) elucidate shared molecular signatures driving disease-induced muscle weakness and ii) apply a translational multi-disease exercise approach to identify novel targets to combat disease-induced muscle weakness. Human subjects and mouse models will undergo functional analyses in vivo and ex vivo, including muscle strength and cellular respirometry. Muscle will undergo additional detailed analyses, including live imaging, single cell profiling and bulk transcriptomics. The molecular signatures will be further elucidated by gain- and loss-of-function experiments in skeletal muscle and by novel in vivo models. The molecular insights will be groundbreaking for our understanding of disease-induced muscle weakness and used for determining future pathways of intervention to ultimately improve muscle function for patients.