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

在整个生命周期中，骨骼肌质量是通过蛋白质代谢的动态变化来调节的，以响应体力活动和营养状态。由于肌原纤维蛋白合成(MPS)和降解(MPB)速率之间的失调，不可避免的短期肌肉骨骼停用(即在受伤/疾病期间)往往伴随着肌肉质量的显著下降。在其他健康的个体中，这些骨骼肌质量的急剧减少主要归因于MPS对运动和营养的钝化反应(称为合成代谢抵抗)，基础MPS在整个停用期间一直处于低迷状态。因此，在理论上，通过控制有效的合成代谢刺激(即身体活动或营养状态)，有可能减弱骨骼肌蛋白质代谢对短期停用期间的负面反应。这个PHD项目将使用细胞到人体的模型，旨在确定三种新的营养成分(亮氨酸、磷脂酸和表儿茶素)在减轻骨骼肌废用性萎缩方面的有效性，并分析支撑骨骼肌蛋白质代谢对这些化合物摄取反应的生物学机制。因此，这项工作可以提供新的和可行的干预措施，以减轻在一生中不可避免的身体缺乏活动的急性时期的骨骼肌萎缩，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.