The effects of human lower limb immobilization on regenerative skeletal muscle stem cell characteristics in vitro

人体下肢固定对体外再生骨骼肌干细胞特性的影响

• 批准号: MR/Y033787/1
• 负责人: Philip Atherton
• 金额: $ 1.24万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY033787%2F1
• 关键词: effects; human; lower; limb; immobilization

Skeletal muscle represents the largest organ and protein reservoir in the human body. Maintenance of skeletal muscle is key for human movement and health. The proteins and DNA containing nuclei within skeletal muscle are constantly being synthesised and degraded. This constant turnover provides an efficient mechanism for the removal of damaged proteins and replacement with new proteins to maintain health.Many situations can negatively impact this balance of protein turnover of skeletal muscle throughout life. These include, the natural ageing process itself, development of chronic diseases more prevalent in later life, malnutrition, trauma, but also "immobilisation", which can be a consequence of enforced bed rest due to hospitalisation, general lack of physical activity, or casting of a leg or arm due to bone fracture. Ultimately this causes loss of muscle size and strength which causes a host of problems, such as weakness and increased risk of falls and development of chronic health conditions.Muscle has within itself a cell than enables regeneration. This cell is called a satellite or stem cell. The aim of this project is to determine the impact of limb (leg) immobilisation - which causes muscle wasting and loss of strength - upon muscle satellite cell function. We hypothesise that extracting these cells from immobilised muscle and examining their behaviour in a laboratory setting will show that immobilisation leads to defects in their function affecting their regenerative capability.This research will have significance to understanding how brief bouts of immobilisation - which commonly occur throughout life - might impact muscle regenerative capacity. We would hope then to seek answers as to how this works and potentially seek therapies to encourage regenerative capacity of these muscle cells that are important to health to improve recovery from bouts of immobilisation.

骨骼肌是人体内最大的器官和蛋白质储存库。骨骼肌的维持是人类运动和健康的关键。骨骼肌中含有细胞核的蛋白质和DNA不断地被合成和降解。这种持续的周转为去除受损的蛋白质和用新的蛋白质替代来维持健康提供了一种有效的机制。许多情况都会对骨骼肌一生中蛋白质周转的平衡产生负面影响。这些因素包括自然衰老过程本身、在晚年更为普遍的慢性疾病的发展、营养不良、创伤，但也包括“瘫痪”，这可能是由于住院、普遍缺乏体力活动或由于骨折而导致腿部或手臂固定而导致的卧床休息的后果。最终，这会导致肌肉大小和力量的丧失，从而导致一系列问题，如虚弱、摔倒的风险增加和慢性健康状况的发展。肌肉本身有一个细胞，可以再生。这种细胞被称为卫星细胞或干细胞。该项目的目的是确定肢体(腿)制动对肌肉卫星细胞功能的影响。肢体(腿)制动会导致肌肉萎缩和力量丧失。我们假设，从固定的肌肉中提取这些细胞并在实验室环境中检测它们的行为将表明，固定会导致它们的功能缺陷，影响它们的再生能力。这项研究将对理解短暂的静止--通常发生在一生中--可能如何影响肌肉的再生能力具有重要意义。然后，我们希望寻求关于这一过程的答案，并可能寻求治疗方法，以鼓励这些对健康至关重要的肌肉细胞的再生能力，以改善从一系列制动中恢复。