Disruption of redox relays in the age-related failure of muscle responses to contractile activity
Disruption of redox relays in the age-related failure of muscle responses to contractile activity
批准号:
MR/P003044/1
负责人:
Malcolm Jackson
金额:
$69.48万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2017
资助国家:
英国
项目状态:
已结题
起止时间:
2017 至 --
中文摘要
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英文摘要
We propose to study the role that a process called a 'redox relay' plays in the response of skeletal muscles to exercise and how this changes with age. Exercise is important in helping to maintain the health of our skeletal muscles and it is well known that skeletal muscle responds to exercise and to other environmental changes in a positive way to make the muscles stronger and work more efficiently. Muscle does this by increasing or decreasing the content of different proteins that are produced after exercise. Unfortunately as we age, these adaptations following exercise become less efficient, increasingly leading to a failure to maintain muscle mass and function.As muscle exercises it generates some very reactive molecules, called reactive oxygen species, and it is known that these species can act as signals to initiate some of the positive adaptations that exercise induces in muscle. Unfortunately the precise way in which these reactive species undertake this is unknown, as is how these actions change as we age. One of these reactive species is hydrogen peroxide which is present in muscles at very low amounts and is the most important of these signalling molecules. Our research team has a great deal of experience of studying hydrogen peroxide and other similar species in muscle and we have previously shown in general terms how important these species are to maintaining muscle integrity following exercise and we also demonstrated that this process appears to become disrupted as we age. Recent studies have shown that a small number of proteins present in our muscles can react with hydrogen peroxide and can transmit an oxidising signal from hydrogen peroxide to other key proteins with which hydrogen peroxide cannot react directly. The process that these intermediary proteins undertake is called a "redox relay" and the proposed project will examine the way that these "redox relay" proteins can transfer the oxidising signal from hydrogen peroxide. It will identify which proteins are able to do this, which other proteins they then react with to transfer the signal and which then go on to stimulate positive adaptations in the muscle. Finally we will determine how this process is modified by ageing. The initial part of the project will involve detailed molecular studies that require us to modify proteins in muscles in order to understand their actions and this will be undertaken in mice. Once we have identified the pathways involved we will then examine key aspects of these that can be measured in muscle biopsy samples that we will obtain from healthy young and older human subjects undertaking exercise. On completion of the project we should understand how these signals are transmitted in muscle following exercise to stimulate positive adaptations in the muscle and how they are changed by ageing and their relevance to the poor responses elderly subjects have to exercise. This information will facilitate the design of logical and targeted interventions to correct the ageing changes with potential benefits of maintaining muscle strength in the elderly.
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Mechanistic models to guide redox investigations and interventions in musculoskeletal ageing.
指导肌肉骨骼衰老的氧化还原研究和干预的机制模型。
DOI:
10.1016/j.freeradbiomed.2020.01.020
发表时间:
2020
期刊:
Free radical biology & medicine
影响因子:
7.4
作者:
[Jackson MJ]
通讯作者:
Jackson MJ
Deletion of Sod1 in Motor Neurons Exacerbates Age-Related Changes in Axons and Neuromuscular Junctions in Mice.
运动神经元中 Sod1 的缺失会加剧小鼠轴突和神经肌肉接头与年龄相关的变化。
DOI:
10.1523/eneuro.0086-22.2023
发表时间:
2023
期刊:
eNeuro
影响因子:
3.4
作者:
[Pollock N]
通讯作者:
Pollock N
DOI:
10.1016/j.freeradbiomed.2020.10.026
发表时间:
2020-12
期刊:
Free radical biology & medicine
影响因子:
7.4
作者:
[Jackson MJ]
通讯作者:
Jackson MJ
DOI:
10.1042/ebc20160088
发表时间:
2017-07
期刊:
Essays in biochemistry
影响因子:
6.4
作者:
[A. Mcardle;M. Jackson]
通讯作者:
A. Mcardle;M. Jackson
DOI:
10.3390/cells11101698
发表时间:
2022-05-20
期刊:
Cells
影响因子:
6
作者:
[]
通讯作者:
共 6 条
HDHL- Combining vitamin E-functionalized chocolate with physical exercise to reduce the risk of protein-energy malnutrition in aged people (CHOKO-AGE)
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批准号:BB/V019821/1
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项目类别:Research Grant
-
资助金额:$34.07万
-
财政年份:2021
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负责人:Malcolm Jackson
-
依托单位:
Close regulation of peroxiredoxin oxidation is essential for maintenance of muscle mass and function in the elderly.
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批准号:MR/V03412X/1
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项目类别:Research Grant
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资助金额:$62.5万
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财政年份:2021
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负责人:Malcolm Jackson
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依托单位:
Liverpool – Confidence in Concept 2019
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批准号:MC_PC_19044
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项目类别:Intramural
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资助金额:$48.86万
-
财政年份:2020
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负责人:Malcolm Jackson
-
依托单位:
BBSRC IAA University of Liverpool
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批准号:BB/S506746/1
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项目类别:Research Grant
-
资助金额:$55.43万
-
财政年份:2018
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负责人:Malcolm Jackson
-
依托单位:
Enhancing Translation at Liverpool through Confidence in Concept
-
批准号:MC_PC_17166
-
项目类别:Intramural
-
资助金额:$37.59万
-
财政年份:2018
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负责人:Malcolm Jackson
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依托单位:
Increasing industry engagement in P4 Medicine: Predictive, Personalised, Preventive & Participatory Medicine
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批准号:MC_PC_17195
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项目类别:Intramural
-
资助金额:$11.34万
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财政年份:2018
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负责人:Malcolm Jackson
-
依托单位:
Centre for Integrated research into Musculoskeletal Ageing (CIMA) Renewal
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批准号:MR/P020941/1
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项目类别:Research Grant
-
资助金额:$166.97万
-
财政年份:2017
-
负责人:Malcolm Jackson
-
依托单位:
Increasing industry engagement & open innovation for personalised health
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批准号:MC_PC_16076
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项目类别:Intramural
-
资助金额:$9.56万
-
财政年份:2017
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负责人:Malcolm Jackson
-
依托单位:
CIMA Centre Students
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批准号:MR/R502182/1
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项目类别:Training Grant
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资助金额:$94.05万
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财政年份:2017
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负责人:Malcolm Jackson
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依托单位:
Role of motor unit remodelling in age-related loss of skeletal muscle fibres.
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批准号:MR/M012573/1
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项目类别:Research Grant
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资助金额:$82.58万
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财政年份:2015
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负责人:Malcolm Jackson
-
依托单位:
University of Liverpool Confidence in Concept Program – Enhancing Translation
-
批准号:MC_PC_14110
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项目类别:Intramural
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资助金额:$38.23万
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财政年份:2015
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负责人:Malcolm Jackson
-
依托单位:
UoLiverpool Confidence in Concept 2013
-
批准号:MC_PC_13068
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项目类别:Intramural
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资助金额:$50.97万
-
财政年份:2014
-
负责人:Malcolm Jackson
-
依托单位:
Denervation of small numbers of fibres during ageing leads to dysregulation of ROS and functional changes in whole skeletal muscles
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批准号:BB/K003860/1
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项目类别:Research Grant
-
资助金额:$45.5万
-
财政年份:2013
-
负责人:Malcolm Jackson
-
依托单位:
CIMA: The Centre for Integrated Research into Musculoskeletal Ageing
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批准号:MR/K006312/1
-
项目类别:Research Grant
-
资助金额:$420.83万
-
财政年份:2012
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负责人:Malcolm Jackson
-
依托单位:
A failure of neuroprotective redox signalling from skeletal muscle to motor neurons leads to loss of motor units with ageing
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批准号:BB/I004076/1
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项目类别:Research Grant
-
资助金额:$46.08万
-
财政年份:2011
-
负责人:Malcolm Jackson
-
依托单位:
Mitochondrial reactive oxygen species as a target for prevention of age-related loss of muscle mass and function
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批准号:G1002120/1
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项目类别:Research Grant
-
资助金额:$55.27万
-
财政年份:2011
-
负责人:Malcolm Jackson
-
依托单位:
Dietary polyphenols as modulators of redox signalling pathways to reduce chronic inflammation in the elderly
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批准号:BB/I005994/1
-
项目类别:Research Grant
-
资助金额:$56.23万
-
财政年份:2011
-
负责人:Malcolm Jackson
-
依托单位:
Site-specific failure of redox homeostasis as a cause of age-related loss of skeletal muscle mass and function
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批准号:G0700919/1
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项目类别:Research Grant
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资助金额:$63.42万
-
财政年份:2008
-
负责人:Malcolm Jackson
-
依托单位:
国内基金
海外基金
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批准号:--
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适度补硒对酒精性肝损伤的拮抗作用及机制研究:Insulin信号调控的Redox稳态和ADH1-ALDH2平衡
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Redox动态变化下潜流带中氯乙酰胺类除草剂转化过程的碳氯同位素解析
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镉致Redox平衡失调氧化损伤的时效、量效与干预机制的研究
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谷胱甘肽及其介导的redox信号调控番茄体内百菌清降解代谢的机理研究
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redox信号介导的6-BA调控黄瓜弱光适应性的生理与分子机制
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