Cell-based models of ageing and disease provide an important platform to probe and extend the mechanistic insights of muscle cell atrophy from invasive and logistically challenging human trials. While cell-based models provide useful insights into the role of metabolic pathways, translation from cell to human can be limited by non-physiological culture conditions, supraphysiological treatment dosages and experimental conditions targeting a single protein, or receptor. Over recent years, there has been an increase in research aimed at improving the physiological relevance of in vitro work, including the use of human plasma and serum. The ex vivo co-culture model has the potential to create a systemic environment representative of ageing and chronic inflammatory disease states. Recent advancements in the application of the ex-vivo co-culture model have highlighted the capacity of human serum to induce atrophy in relation to its host environment. We, and others have utilised the human serum and plasma from young and old males, to investigate ageing-related cellular atrophy (Kalampouka et al., 2018; Allen et al., 2021) and chronic liver disease patients to investigate disease related atrophy (Allen et al., 2022). This talk will describe the effects of young and old ex vivo serum on cellular growth and protein stasis, before outlining the utility of the ex-vivo model to investigate muscle atrophy in chronic inflammatory disease conditions e.g., chronic liver disease and rheumatoid arthritis.