Understanding Muscle Growth Responses to Nutrition in Adult Survivors of Childhood Acute lymphoblastic Leukaemia

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase.

Project Information

Research Theme: Population Health Sciences

Summary: Survivors of childhood acute lymphoblastic leukaemia (ALL) experience premature frailty and muscle atrophy. Muscle protein synthesis is crucial for muscle growth and is mainly stimulated by physical activity and dietary protein. Since dietary protein intakes in ALL survivors do not differ from the general population, it is suggested that the observed muscle atrophy is caused by an inability of muscle growth to respond normally to dietary stimuli, termed anabolic resistance. This PhD will mechanistically explore if anabolic resistance underlies frailty in ALL survivors in response to diet, and design tailored dietary and exercise interventions to promote muscle growth.

Project Description:

Sixty percent childhood Acute Lymphoblastic Leukaemia (ALL) survivors experience frailty 25 years before the general population (44 vs. 69 years) (Smitherman et al. 2020). Frailty, defined as muscle atrophy, exhaustion/low energy expenditure and weakness (Fried et al. 2001), leads to more comorbidities, relapse, and death (Ness et al 2013). Skeletal muscle mass is determined by the balance of protein muscle synthesis (MPS) and breakdown. MPS is stimulated by exercise and dietary protein and is considered a predominant component that dictates muscle growth (Davies et al. 2020). Protein intakes in ALL survivors do not differ from the general population (Belle et al 2017) suggesting an inability of MPS to respond normally to dietary stimuli, termed anabolic resistance. Indeed, anabolic resistance is a primary driver for muscle loss with age and inflammatory conditions. We showed that anabolic resistance may be driving muscle loss in Crohn’s disease, which has a similar muscle phenotype to ALL (Davies et al 2021). Studies investigating if anabolic resistance is a pathophysiology mechanism of frailty and dietary strategies designed to ameliorate frailty in ALL survivors are lacking. This project will measure muscle protein balance in childhood ALL survivors and matched-healthy controls in the fasted and fed states together with inflammatory and functional readouts to provide holistic muscle phenotypes. The results will be used by the PhD student to devise and test various nutrition (e.g. protein) or exercise strategies to promote MPS in subsequent studies.

Advert information