Grant: Master's Award: Canada Graduate Scholarships

The muscle loss observed during aging (sarcopenia) and in cancer-associated cachexia is detrimental as it reduces the patient's physical function, autonomy, responses to therapy, immune responses, quality and duration of life. It could be due to impaired action of insulin in stimulating muscle protein synthesis (PS) and in suppressing breakdown (PB). Both components need to be measured to establish protein balance or net anabolism, but current in vivo techniques to measure muscle PB are too invasive to use in frail subjects. Our objectives are 1) to measure total and skeletal muscle myofibrillar PB in response to high insulin levels, using the dilution of a stable isotope, in healthy humans with the aim of validating a new approach to be used as a non-invasive technique in frail patients and 2) to relate acute changes in muscle PB to the expression of protein and genes of a major proteolytic system in the muscle cells. This initial study will establish the validity of estimating muscle PB from a surrogate measure in plasma, which would thereafter preclude the need for muscle biopsies and thus be less invasive to use in frail patients. We can then apply this approach in conditions of increased catabolism and/or impaired anabolism, in aging and cancer cachexia, to help unravel the mechanisms of the associated muscle loss.