Muscle Activity and Growth: from Developmental Genetics to the Human Population

肌肉活动和生长:从发育遗传学到人类

基本信息

  • 批准号:
    MR/W001381/1
  • 负责人:
  • 金额:
    $ 180.47万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2022
  • 资助国家:
    英国
  • 起止时间:
    2022 至 无数据
  • 项目状态:
    未结题

项目摘要

Muscle mass affects us throughout our lives. It is a major predictor of bone strength, sporting performance, career choice, propensity to obesity and diabetes and the development of debilitating muscle weakening in the elderly, which often leads to physical dependency. We know that people differ in muscle mass at birth due to genetic, epigenetic and environmental factors that impinge on mother and child during pregnancy. Although muscle grows hugely after birth, there is a strong correlation between muscle mass at birth and in later life. Muscle is made from several kinds of stem cells formed in the early embryo, yet how muscle mass is determined during prenatal life is unclear. This proposal aims to find out by understanding the fundamental cell and molecular biological processes that control the size of muscle tissue in a simple system.Skeletal muscle approaches 30-40% of human body mass, depending on sex and age. In addition to one's endowment at birth, physical activity during childhood and adolescence is thought to influence adult muscle mass, contractile properties and the balance between muscle and fat, which is a major predictor of healthspan. Measures of muscle/fat ratio correlate negatively with incidence of type 2 diabetes, coronary heart disease, stroke, colon, breast and other cancers, fatty-liver disease, osteoarthritis, age-related muscle wasting and, of course, obesity. Although cause and effect are debated in these correlations, there is a consensus that a more 'athletic' physique (i.e. higher muscle/fat ratio) is likely to improve the health and outlook for a significant fraction of the population, with consequent economic and quality of life benefits for society as a whole.It is clear that 'environmental' effects, like exercise and food consumption, help to control muscle mass, but they work on the tissue formed during earlier life. Emerging evidence indicates that exercise has long-term influences on whole body metabolism not just due to direct training effects on muscle itself, but also because exercised muscle releases signals that control growth of fat, heart and other tissues. There is thus a need to understand how muscle mass is controlled and affected by physical activity, diet etc. Our recent findings show that very early muscle tissue requires physical activity for normal growth, grows differently in day and night, is influenced by nutrition and, within limits, has a remarkable ability to regulate its mass. We have also developed methods of watching the formation and growth of muscle from several distinct populations of stem cells in the living animal. This proposal aims:1) To understand the molecular mechanism(s) by which physical activity controls muscle growth. Our study, while aimed at fundamental insight into development, will also reveal mechanisms by which training builds muscle in the elderly, athletes and for general health. By understanding how contraction regulates muscle growth, the work will shed light on how force controls cell behaviour more generally.2) To discover how individual muscle cells are formed and grow. Muscle tissue balances proliferation and differentiation of stem cells to control formation of the correct number of muscle fibres and their subsequent growth. By providing understanding of how muscle is built, our studies will reveal how genes and early life experience interact to generate the muscular 'starting point', which, together with the vicissitudes of later life, controls general health and the onset of age-related diseases.3) To study, in a simple model system, how lifestyle choices like exercise, shift-work and eating habits are integrated by genetic predisposition(s) to control muscle growth.4) To apply our growing understanding of the gene/environment interaction in simple systems to the UK population by using the UK Biobank to elucidate factors driving ageing-related muscle weakening. Our long-term aim is personalised lifestyle advice.
肌肉质量会影响我们的一生。它是骨骼强度、运动表现、职业选择、肥胖和糖尿病倾向以及老年人肌肉衰弱的主要预测因素,肌肉衰弱往往导致身体依赖。我们知道,由于遗传、表观遗传和环境因素,人们在出生时的肌肉质量不同,这些因素会在怀孕期间影响母亲和孩子。虽然肌肉在出生后会长得很大,但出生时的肌肉质量与以后的生活有很强的相关性。肌肉是由早期胚胎中形成的几种干细胞组成的,但在产前生活中肌肉质量是如何确定的尚不清楚。该提案旨在通过了解在一个简单的系统中控制肌肉组织大小的基本细胞和分子生物学过程来找出答案。骨骼肌接近人体质量的30-40%,取决于性别和年龄。除了一个人出生时的禀赋之外,儿童和青少年时期的体育活动被认为会影响成年后的肌肉质量、收缩特性以及肌肉和脂肪之间的平衡,这是健康寿命的主要预测因素。肌肉/脂肪比的测量与2型糖尿病、冠心病、中风、结肠癌、乳腺癌和其他癌症、脂肪肝、骨关节炎、年龄相关的肌肉萎缩以及肥胖的发病率呈负相关。尽管这些相关性的因果关系还在争论中,但有一个共识是,(即更高的肌肉/脂肪比例)可能会改善相当一部分人口的健康和前景,从而为整个社会带来经济和生活质量方面的好处。很明显,“环境”效应,如运动和食物消费,有助于控制肌肉质量,但它们作用于生命早期形成的组织。新出现的证据表明,运动对全身新陈代谢有长期影响,这不仅是因为运动对肌肉本身的直接影响,还因为运动的肌肉释放出控制脂肪、心脏和其他组织生长的信号。因此,有必要了解肌肉质量是如何控制和影响的身体活动,饮食等,我们最近的研究结果表明,非常早期的肌肉组织需要身体活动的正常增长,在白天和黑夜不同的增长,是受营养的影响,并在一定范围内,有一个显着的能力来调节其质量。我们还开发了观察活体动物中几种不同干细胞群体肌肉形成和生长的方法。本提案旨在:1)了解身体活动控制肌肉生长的分子机制。我们的研究,虽然旨在对发展的基本见解,也将揭示训练在老年人,运动员和一般健康中建立肌肉的机制。通过了解收缩如何调节肌肉生长,这项工作将揭示力如何更普遍地控制细胞行为。2)发现单个肌肉细胞如何形成和生长。肌肉组织平衡干细胞的增殖和分化,以控制正确数量的肌纤维的形成及其随后的生长。通过了解肌肉是如何构建的,我们的研究将揭示基因和早期生活经历如何相互作用以产生肌肉“起点”,该起点与晚年生活的变迁一起控制总体健康状况和年龄相关疾病的发生。3)在一个简单的模型系统中研究运动等生活方式的选择,轮班工作和饮食习惯通过遗传倾向来控制肌肉生长。4)通过使用英国生物库来阐明驱动与衰老相关的肌肉衰弱的因素,将我们对简单系统中基因/环境相互作用的日益理解应用于英国人群。我们的长期目标是个性化的生活方式建议。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespan
整个脊椎动物生命周期中肌源性前体细胞的克隆行为
  • DOI:
    10.1101/2022.02.17.480906
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hughes S
  • 通讯作者:
    Hughes S
Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespan.
  • DOI:
    10.1242/bio.059476
  • 发表时间:
    2022-08-15
  • 期刊:
  • 影响因子:
    2.4
  • 作者:
    Hughes, Simon M.;Escaleira, Roberta C.;Wanders, Kees;Koth, Jana;Wilkinson, David G.;Xu, Qiling
  • 通讯作者:
    Xu, Qiling
Slow myosin heavy chain 1 is required for slow myofibril and muscle fibre growth but not for myofibril initiation.
  • DOI:
    10.1016/j.ydbio.2023.04.002
  • 发表时间:
    2023-07
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Hau, Hoi-Ting A.;Kelu, Jeffrey J.;Ochala, Julien;Hughes, Simon M.
  • 通讯作者:
    Hughes, Simon M.
Skeletal Muscle Regeneration in Zebrafish.
斑马鱼的骨骼肌再生。
Isolation, Culture, and Analysis of Zebrafish Myofibers and Associated Muscle Stem Cells to Explore Adult Skeletal Myogenesis.
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Simon Hughes其他文献

The use of the Baumber scoring system for metastatic disease of the vertebral column
  • DOI:
    10.1186/s13104-025-07390-1
  • 发表时间:
    2025-07-22
  • 期刊:
  • 影响因子:
    1.700
  • 作者:
    Sam Hodgson;Paul Pynsent;Simon Hughes;Petr Rehousek;Adrian Gardner
  • 通讯作者:
    Adrian Gardner
FDG PETCT analysis of 146 Individual DIPNECH pulmonary nodules
  • DOI:
    10.1016/j.crad.2019.09.051
  • 发表时间:
    2019-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Krishan Odedra;Simon Hughes
  • 通讯作者:
    Simon Hughes
537 Planning feasibility study for HDR-brachytherapy to treat muscle invasive bladder cancer
537 用于治疗肌层浸润性膀胱癌的高剂量率近距离放射治疗的规划可行性研究
  • DOI:
    10.1016/s0167-8140(25)04224-0
  • 发表时间:
    2025-05-01
  • 期刊:
  • 影响因子:
    5.300
  • 作者:
    Liam Mannion;Emma-Louise Jones;Jeyaanth Venkatasai;Simon Hughes;Vinod Mullassery
  • 通讯作者:
    Vinod Mullassery
Posterior instrumented fusion for thoracolumbar kyphosis in mucopolysaccharidoses type 1
  • DOI:
    10.1016/j.spinee.2016.01.058
  • 发表时间:
    2016-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Neil Oxborrow;Thomas Finnigan;Ian McLaughlin;Simon Hughes
  • 通讯作者:
    Simon Hughes
Bmc Molecular Biology the Use of Multiple Displacement Amplified Dna as a Control for Methylation Specific Pcr, Pyrosequencing, Bisulfite Sequencing and Methylation-sensitive Restriction Enzyme Pcr
Bmc Molecular Biology 使用多重置换扩增 DNA 作为甲基化特异性 PCR、焦磷酸测序、亚硫酸氢盐测序和甲基化敏感限制性酶 PCR 的对照
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Simon Hughes;J. L. Jones
  • 通讯作者:
    J. L. Jones

Simon Hughes的其他文献

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{{ truncateString('Simon Hughes', 18)}}的其他基金

Mechanisms of activity-dependent muscle growth and repair
活动依赖性肌肉生长和修复的机制
  • 批准号:
    MR/N021231/1
  • 财政年份:
    2016
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Research Grant
Role of mRNA localisation and translational control in muscle growth
mRNA 定位和翻译控制在肌肉生长中的作用
  • 批准号:
    BB/K010115/1
  • 财政年份:
    2013
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Research Grant
Somitic muscle growth: a new model for the role of force in morphogenesis
体节肌肉生长:力在形态发生中作用的新模型
  • 批准号:
    G1001029-E01/1
  • 财政年份:
    2011
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Research Grant

相似海外基金

Mechanisms of activity-dependent muscle growth and repair
活动依赖性肌肉生长和修复的机制
  • 批准号:
    MR/N021231/1
  • 财政年份:
    2016
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Research Grant
Immune system involvement in skeletal muscle adaptation to contractile activity during human growth
免疫系统参与人体生长过程中骨骼肌对收缩活动的适应
  • 批准号:
    341353-2007
  • 财政年份:
    2011
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Discovery Grants Program - Individual
Immune system involvement in skeletal muscle adaptation to contractile activity during human growth
免疫系统参与人体生长过程中骨骼肌对收缩活动的适应
  • 批准号:
    341353-2007
  • 财政年份:
    2010
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Discovery Grants Program - Individual
Immune system involvement in skeletal muscle adaptation to contractile activity during human growth
免疫系统参与人体生长过程中骨骼肌对收缩活动的适应
  • 批准号:
    341353-2007
  • 财政年份:
    2009
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Discovery Grants Program - Individual
Immune system involvement in skeletal muscle adaptation to contractile activity during human growth
免疫系统参与人体生长过程中骨骼肌对收缩活动的适应
  • 批准号:
    341353-2007
  • 财政年份:
    2008
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Discovery Grants Program - Individual
Immune system involvement in skeletal muscle adaptation to contractile activity during human growth
免疫系统参与人体生长过程中骨骼肌对收缩活动的适应
  • 批准号:
    341353-2007
  • 财政年份:
    2007
  • 资助金额:
    $ 180.47万
  • 项目类别:
    Discovery Grants Program - Individual
ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE
活动引起骨骼肌生长
  • 批准号:
    3160880
  • 财政年份:
    1990
  • 资助金额:
    $ 180.47万
  • 项目类别:
ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE
活动引起骨骼肌生长
  • 批准号:
    2080082
  • 财政年份:
    1990
  • 资助金额:
    $ 180.47万
  • 项目类别:
ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE
活动引起骨骼肌生长
  • 批准号:
    3160882
  • 财政年份:
    1990
  • 资助金额:
    $ 180.47万
  • 项目类别:
ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE
活动引起骨骼肌生长
  • 批准号:
    3160879
  • 财政年份:
    1990
  • 资助金额:
    $ 180.47万
  • 项目类别:
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