The role of integrins in muscle stem cell function

男性和女性在晚年会失去50%的骨骼肌质量，这是一种称为年龄相关性肌肉减少症的过程，其特征是肌肉质量、耐力和力量的综合损失。这导致活动能力逐渐丧失，最终导致年老时身体虚弱和丧失独立能力。由于英国人口结构的变化，预计80岁及以上的人口在未来20年将翻一番，因此有必要研究与年龄相关的肌肉减少症的机制，这可能导致旨在减少肌肉损失的干预策略。卫星细胞是常驻骨骼肌干细胞，也是肌肉修复的主要贡献者，无论是在受伤后还是在肌肉萎缩性疾病中。卫星细胞是静止的肌源性干细胞，其在损伤时迅速活化。卫星细胞库及其增殖能力随着年龄的增长而减少，最终导致有缺陷的肌肉维护和修复。卫星细胞嵌入在肌纤维的基底膜和质膜之间的专门龛中。然而，很少有人知道这个小生境在调节SC的激活和自我更新中起什么作用，或者与年龄相关的改变可能导致肌肉损失。该项目将使用体内和体外实验来确定两种整合素的作用，整合素a7和a5，卫星细胞行为，以及离体单肌纤维测定，并研究当卫星细胞表达的这些跨膜受体不存在时受到干扰的细胞过程。

Men and women lose 50% of their skeletal muscle mass in later life through a process called age-related sarcopenia, characterised by a combined loss of muscle mass, endurance and strength. This results in progressive loss in mobility eventually leading to frailty and loss of independence in old age. Because of the changing demographics in the UK, where the population aged 80 years and older is predicted to double over the next 20 years, there is a need to study mechanisms of age-related sarcopenia, which can lead to intervention strategies designed to reduce muscle loss.Satellite cells are the resident skeletal muscle stem cells and the main contributors to muscle repair, either after injury or in muscle wasting diseases. Satellite cells are quiescent myogenic stem cells, which become rapidly activated upon injury. The satellite cell pool and its proliferative capacity diminish with age, eventually leading to defective muscle maintenance and repair. Satellite cells are embedded in a specialised niche between the basement membrane and the plasma membrane of the muscle fibre. However, little is known what role this niche plays in regulating activation and self-renewal of SCs, or age-related alterations that may contribute to muscle loss.The project will use in vivo and in vitro experiments to define the role of two integrins, integrin a7 and a5, for satellite cell behaviour, as well as ex vivo single muscle fibre assays and investigate the cellular processes that are perturbed when these transmembrane receptors expressed by satellite cells are absent.