Greater loss of mitochondrial function with ageing s associated with earlier onset of sarcopenia in C. elegans
Greater loss of mitochondrial function with ageing s associated with earlier onset of sarcopenia in C. elegans
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DOI：
10.18632/aging.101654
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发表时间：
2018-11-01
期刊：
影响因子：
5.2
通讯作者：
Szewczyk, Nathaniel J.
中科院分区：
文献类型：
--
作者：
Gaffney, Christopher J.;Pollard, Amelia;Szewczyk, Nathaniel J.
肌肉减少症是一种与年龄有关的肌肉衰退，是一种日益严重的重大公共卫生负担。秀丽隐杆线虫是一种研究衰老机制的模式生物，也表现出肌肉减少症，但其潜在的机制仍然难以捉摸。在这里，我们使用秀丽隐杆线虫对温度的自然缩放寿命来研究线粒体含量、线粒体功能和肌肉减少症之间的关系。线粒体含量和最大线粒体ATP生成率（MAPR）与寿命呈反比关系，而MAPR下降的开始与寿命呈正相关。肌肉线粒体结构、肌节结构和运动能力下降也显示出与寿命的直接关系。值得注意的是，线粒体网络结构的下降比肌节的下降发生得更早，并且与运动能力的丧失有更强的相关性，并且与寿命有关。这些结果表明，线粒体功能在衰老过程中至关重要，并且比肌节结构的丧失更能解释肌肉减少症的发生和进展。
Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here, we use C. elegans natural scaling of lifespan in response to temperature to examine the relationship between mitochondrial content, mitochondrial function, and sarcopenia. Mitochondrial content and maximal mitochondrial ATP production rates (MAPR) display an inverse relationship to lifespan, while onset of MAPR decline displays a direct relationship. Muscle mitochondrial structure, sarcomere structure, and movement decline also display a direct relationship with longevity. Notably, the decline in mitochondrial network structure occurs earlier than sarcomere decline, and correlates more strongly with loss of movement, and scales with lifespan. These results suggest that mitochondrial function is critical in the ageing process and more robustly explains the onset and progression of sarcopenia than loss of sarcomere structure.