The regulation of muscle stem cell migration in ageing

西方社会个人寿命的延长将给发达国家的医疗和经济体系带来相当大的挑战，因为他们照顾的是身体机能因年龄而恶化的人。衰老与骨骼肌质量的进行性减少有关，这一过程称为骨质疏松症。与年龄相关的肌肉丧失导致肌肉力量不足，导致姿势和活动能力降低，摔倒风险增加，所有这些都会导致生活质量下降。骨骼肌含有干细胞，在年轻人身上能够维持质量。老化的肌肉中含有干细胞，但这些干细胞不能维持质量。我们最近发现，衰老的肌肉干细胞的移动速度比年轻的干细胞慢得多，并假设迁移能力在修复过程中至关重要。重要的是，我们发现一氧化氮，一种强大的细胞信号分子，使年老的肌肉细胞干细胞能够以年轻细胞的速度移动。在这项研究中，我们的目标是确定小鼠何时出现迁移速度缺陷，以及这与肌肉中一氧化氮水平的变化有何关联。然后，我们将优化提高肌肉中一氧化氮水平的方法，并将其与肌肉干细胞迁移速度的变化联系起来。最后，我们将使用本方案前面所有部分产生的数据来开发一种增加老化肌肉中一氧化氮的方法，并确定它是否改善肌肉修复过程。我们的目标是证明使用一氧化氮增加肌肉干细胞迁移可以提高修复速度。值得注意的是，一些提高一氧化氮水平的药物已经被批准用于人类。因此，我们的研究结果有可能被迅速转化为预防人类与年龄相关的肌肉损失的方法。

The increase in the longevity of individuals in Western societies will present considerable challenges to the healthcare and economic systems of developed countries as they care for people whose body functions undergo age-related deterioration. Old age is associated with a progressive loss of skeletal muscle mass, a process called sarcopenia. Aged related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility, increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle contains stem cells that in the young are able to maintain mass. Aged muscle contains stem cells but these are not able to maintain mass. We have recently shown that aged muscle stem cells move considerably slower than young stem cells and postulate that the ability to migrate is crucial in the repair process. Importantly we found that Nitric Oxide, a powerful cell signalling molecule, enabled old muscle cells stem to move at speeds of young cells. In this investigation we aim to determine when mice develop deficits in migration speeds and how this correlates with changes in Nitric Oxide levels in muscle. We will then optimise the means of increasing Nitric Oxide levels in muscle and relate these to changes in muscle stem cell migration speeds. Finally we will use data generated from all previous section of this package to develop a regime that increases Nitric Oxide in aged muscle and determine whether it improves the muscle repair process.We aim to show that increasing muscle stem cell migration using Nitric Oxide results in an enhanced rate of repair. Significantly, a number of drugs that increase Nitric Oxide levels have already been approved for use in humans. Therefore it is possible that results of our study could be rapidly translated into regimes to prevent age related muscle loss in humans.