The regulation of muscle stem cell migration in ageing

衰老过程中肌肉干细胞迁移的调节

• 批准号: BB/J016454/1
• 负责人: Ketan Patel
• 金额: $ 41.82万
• 依托单位: University of Reading
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ016454%2F1
• 关键词: regulation; muscle; stem; cell; migration

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.

西方社会中个人寿命的增加将对发达国家的医疗保健和经济体系提出相当大的挑战，因为他们照顾身体功能经历与年龄相关的恶化的人。老年与骨骼肌质量的逐渐丧失有关，这一过程称为肌肉减少症。与年龄相关的肌肉损失导致肌肉力量缺乏，导致姿势和活动性降低，福尔斯风险增加，所有这些都导致生活质量下降。骨骼肌含有干细胞，在年轻时能够保持质量。衰老的肌肉含有干细胞，但这些干细胞不能维持质量。我们最近发现，老年肌肉干细胞比年轻干细胞移动得慢得多，并假设迁移能力在修复过程中至关重要。重要的是，我们发现一氧化氮是一种强大的细胞信号分子，能够使老年肌肉细胞以年轻细胞的速度运动。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变化的关系。然后，我们将优化增加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，我们将使用从本包的所有前面部分生成的数据来开发一个制度，增加一氧化氮在老化的肌肉，并确定它是否改善肌肉修复过程。我们的目的是表明，增加肌肉干细胞迁移使用一氧化氮的结果在修复率提高。值得注意的是，一些增加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迅速转化为预防人类年龄相关肌肉损失的方案。

项目成果

Link between MHC Fiber Type and Restoration of Dystrophin Expression and Key Components of the DAPC by Tricyclo-DNA-Mediated Exon Skipping.

• DOI: 10.1016/j.omtn.2017.10.014
• 发表时间: 2017-12-15
• 期刊: Molecular therapy. Nucleic acids
• 作者: Omairi S;Hau KL;Collin-Hooper H;Montanaro F;Goyenvalle A;Garcia L;Patel K
• 通讯作者: Patel K

Characterisation of Development and Electrophysiological Mechanisms Underlying Rhythmicity of the Avian Lymph Heart.

• DOI: 10.1371/journal.pone.0166428
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Jaffer S;Valasek P;Luke G;Batarfi M;Whalley BJ;Patel K
• 通讯作者: Patel K

Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation.

• DOI: 10.1371/journal.pone.0120524
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Collins-Hooper H;Sartori R;Giallourou N;Matsakas A;Mitchell R;Makarenkova HP;Flasskamp H;Macharia R;Ray S;Swann JR;Sandri M;Patel K
• 通讯作者: Patel K

Investigating the Influence of Extracellular Matrix and Glycolytic Metabolism on Muscle Stem Cell Migration on Their Native Fiber Environment

研究细胞外基质和糖酵解代谢对肌肉干细胞迁移对其天然纤维环境的影响

• DOI: 10.3390/fib3030253
• 发表时间: 2015
• 期刊: Fibers
• 影响因子: 3.9
• 作者: Butera G

Mammalian Skeletal Muscle Fibres Promote Non-Muscle Stem Cells and Non-Stem Cells to Adopt Myogenic Characteristics

哺乳动物骨骼肌纤维促进非肌肉干细胞和非干细胞采用生肌特征

• DOI: 10.3390/fib5010005
• 发表时间: 2017
• 期刊: Fibers
• 影响因子: 3.9
• 作者: Morash T