Skeletal muscle comprises ~ 45% of the healthy human body mass. It is critical for development, growth, metabolism, posture, locomotion, thermoregulation and the provision of energy. Ageing, muscular dystrophies and cachexia are associated with muscle wasting and weakness, however, the mechanisms underpinning these losses may differ. Muscles hypertrophy (increase in size through an increase in the cross sectional area of individual fibres) when protein synthesis exceeds protein degradation, in response to e.g. loading, which ultimately leads to an increase in maximal force generating capacity. Conversely, muscles atrophy (decline in fibre size and cross sectional area) following disuse, unloading or disease, which culminates in a decline in peak force generating capacity – when protein degradation dominates. The adaptability of skeletal muscle, given its terminally differentiated state, is thought to be achieved via activation of resident muscle stem cells. The regulators of synthesis, degradation and ultimately muscle mass are therefore likely to involve complex cellular, biochemical and genetic controllers. Our research focuses on using and developing stem cell cultures to model the interactions of skeletal muscle cells with anabolic (insulin-like growth factors) and catabolic (tumour necrosis factor-alpha, interleukin-6) agents. Models span age, disease and injury and provide us with a means to understand the regulators (e.g. IGFBPs, PI3 kinase, MAP kinase, Adra1d, caspases and sirtuins), which influence survival, differentiation, migration or death of these cells. Key human studies complement our work (age, nutrition and exercise) and are critical, since severe loss of functional muscle mass contributes to increased morbidity and early mortality. This presentation will provide information on the use of our model systems to provide some insight into the regulators of muscle adaptation.