Determining the effectiveness of novel nutraceutical compounds to support skeletal muscle proteostasis during ageing and disuse.

Throughout the lifespan, skeletal muscle mass is regulated through dynamic changes in protein metabolism in response to physical activity and nutritional status. Short-term periods of unavoidable musculoskeletal disuse (i.e. during injury/illness) are often accompanied by significant declines in muscle mass due to a dysregulation between myofibrillar protein synthesis (MPS) and degradation (MPB) rates. In otherwise healthy individuals, these acute decrements to skeletal muscle mass are primarily attributed to a blunted response of MPS to exercise and nutrition (termed 'anabolic resistance'), with basal MPS remaining depressed throughout the disuse episode. Therefore, in theory, by manipulating potent anabolic stimuli (i.e. physical activity or nutritional status), it is possible to attenuate the negative response of skeletal muscle protein metabolism to periods of short-term disuse. This PhD project will use a cell-to-human model that aims to determine the effectiveness of three novel nutraceutical compounds (leucine, phosphatidic acid and epicatechin) to attenuate skeletal muscle disuse atrophy and analyse the biological mechanisms that underpin the response of skeletal muscle protein metabolism to the ingestion of these compounds. Consequently, this work could provide novel and feasible interventions to attenuate skeletal muscle atrophy during acute periods of unavoidable physical inactivity throughout the lifespan, thus prolonging an individual's health span.