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

在整个生命周期中，骨骼肌质量通过蛋白质代谢的动态变化来调节，以响应身体活动和营养状况。由于肌原纤维蛋白合成（MPS）和降解（MPB）速率之间的失调，不可避免的肌肉骨骼废用的短期（即在损伤/疾病期间）通常伴随着肌肉质量的显著下降。在其他健康个体中，骨骼肌质量的这些急性减少主要归因于MPS对运动和营养的迟钝反应（称为“合成代谢抵抗”），在整个废用期基础MPS保持抑制。因此，在理论上，通过操纵有效的合成代谢刺激（即体力活动或营养状况），可以减弱骨骼肌蛋白质代谢对短期废用期的负面反应。该博士项目将使用细胞对人类模型，旨在确定三种新型营养化合物（亮氨酸，磷脂酸和表儿茶素）减轻骨骼肌废用性萎缩的有效性，并分析支撑骨骼肌蛋白质代谢对这些化合物摄入的反应的生物学机制。因此，这项工作可以提供新的和可行的干预措施，以减轻骨骼肌萎缩在急性期不可避免的身体活动在整个生命周期，从而延长个人的健康寿命。

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.