Mechanistic models to guide redox investigations and interventions in musculoskeletal ageing.
Mechanistic models to guide redox investigations and interventions in musculoskeletal ageing.
复制标题
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
复制
发表时间：
2020
影响因子：
7.4
通讯作者：
Jackson MJ
中科院分区：
文献类型：
--
作者：
Jackson MJ
年龄是主要慢性肌肉骨骼疾病、骨关节炎、骨质疏松症以及与年龄相关的骨骼肌质量和功能丧失（肌肉减少症）的最大风险因素。人们正在利用对衰老过程基本机制的理解方面取得的巨大进展来了解这些与年龄有关的疾病的原因，并确定预防或治疗这些疾病的方法。这篇综述将集中在这些基本机制之一，氧化还原调节，和氧化还原变化的作用，与年龄相关的骨骼肌质量和功能的损失（少肌症）。了解这些途径的作用的关键是开发和研究肌肉骨骼衰老的实验模型，这些模型旨在研究ROS调节酶的修饰效果。这些主要涉及小鼠中ROS调节酶的基因缺失。研究的许多模型均显示组织氧化损伤增加，但尚未发现与骨骼肌衰老的明确关系。例外的是超氧化物歧化酶被破坏的小鼠，特别是位于细胞质中的Cu，ZnSOD（SOD 1）缺失。和线粒体膜间隙。对缺乏SOD 1的组织特异性模型的研究强调了氧化还原途径中断在肌肉损失和虚弱中的潜在作用，并证明了研究运动神经元和肌肉以了解骨骼肌年龄相关损失的必要性。运动神经元和骨骼肌中氧化还原稳态的变化及其在肌肉质量和功能过早丧失中的作用之间的复杂相互作用已被确定，说明了可修改模型的实用性，以建立可能导致年龄相关变化的关键途径，并确定潜在的逻辑干预方法。
Age is the greatest risk factor for the major chronic musculoskeletal disorders, osteoarthritis, osteoporosis and age-related loss of skeletal muscle mass and function (sarcopenia). Dramatic advances in understanding of the fundamental mechanisms underlying the ageing process are being exploited to understand the causes of these age-related disorders and identify approaches to prevent or treat these disorders. This review will focus on one of these fundamental mechanisms, redox regulation, and the role of redox changes in age-related loss of skeletal muscle mass and function (sarcopenia). Key to understanding the role of such pathways has been the development and study of experimental models of musculoskeletal ageing that are designed to examine the effect of modification of ROS regulatory enzymes. These have primarily involved genetic deletion of regulatory enzymes for ROS in mice. Many of the models studied show increased oxidative damage in tissues, but no clear relationship with skeletal muscle aging has been seen The exception to this has been mice with disruption of the superoxide dismutases and, in particular, deletion of Cu,ZnSOD (SOD1) localised in the cytosol and mitochondrial intermembrane space. Studies of tissue specific models lacking SOD1 have highlighted the potential role that disrupted redox pathways can play in muscle loss and weakness and have demonstrated the need to study both motor neurons and muscle to understand age-related loss of skeletal muscle. The complex interplay that has been identified between changes in redox homeostasis in the motor neuron and skeletal muscle and their role in premature loss of muscle mass and function illustrates the utility of modifiable models to establish key pathways that may contribute to age-related changes and identify potential logical approaches to intervention.
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DOI：
10.1196/annals.1323.002
发表时间：
2005-01-01
期刊：
LONGEVITY HEALTH SCIENCES: THE PHOENIX CONFERENCE
影响因子：
--
作者：
Yoshida, T;Nakamura, H;Yodoi, J
通讯作者：
Yodoi, J
影响因子：
5.5
作者：
Lustgarten, Michael S.;Jang, Youngmok C.;Van Remmen, Holly
通讯作者：
Van Remmen, Holly
一氧化氮、超氧化物和过氧亚硝酸盐：好的、坏的和丑陋的。
DOI：
10.1152/ajpcell.1996.271.5.c1424
发表时间：
1996
期刊：
The American journal of physiology
影响因子：
--
作者：
Beckman,JS;Koppenol,WH
通讯作者：
Koppenol,WH
影响因子：
13.1
作者：
da Costa JP;Vitorino R;Silva GM;Vogel C;Duarte AC;Rocha-Santos T
通讯作者：
Rocha-Santos T
影响因子：
7.4
作者：
Mecocci, P;Fanó, G;Beal, MF
通讯作者：
Beal, MF