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

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:
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
项目状态:
未结题
起止时间:
2024 至 --

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中文摘要
翻译
骨骼肌是人体最大的器官和蛋白质储存库。骨骼肌的维持是人体运动和健康的关键。骨骼肌内含有细胞核的蛋白质和DNA不断地被合成和降解。这种不断的周转提供了一种有效的机制,用于清除受损的蛋白质并替换新的蛋白质以维持健康。许多情况会对骨骼肌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、晚年更普遍的慢性疾病的发展、营养不良、创伤,但也包括“固定”,这可能是由于住院、一般缺乏体力活动或由于骨折导致腿或手臂骨折而被迫卧床休息的结果。最终,这会导致肌肉大小和力量的损失,从而导致一系列问题,如虚弱和增加福尔斯和慢性健康状况的发展风险。肌肉本身有一个细胞比能够再生。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)固定-导致肌肉萎缩和力量损失-对肌肉卫星细胞功能的影响。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查它们的行为将表明,固定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固定-这通常发生在整个生命中-可能如何影响肌肉再生能力具有重要意义。然后,我们希望寻求关于这是如何工作的答案,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,以改善从固定中恢复的能力。
英文摘要
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.
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