Dulac Maude, Hajj-Boutros Guy, Sonjak Vita, Faust Andréa, Hussain Sabah N A, Chevalier Stéphanie, Dionne Isabelle J, Morais José A, Gouspillou Gilles
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
J Physiol. 2024 Jun 15. doi: 10.1113/JP285897.
Mitochondrial dysfunctions are thought to contribute to muscle atrophy and weakness that develop during ageing and mechanical unloading caused by immobilization, bed rest and microgravity. Older adults are at greater risk of developing muscle and mitochondrial dysfunctions in response to unloading. Although exercise is well known to promote muscle and mitochondrial health, its protective effect during mechanical unloading in older adults remains largely unexplored. Here, we investigated the impact of 14 days of head-down tilt bed rest (HDBR) with and without a multimodal exercise countermeasure in older men and women (55-65 years). Leg muscle volume was assessed using magnetic resonance imaging. Biopsies of the vastus lateralis were performed to assess markers of mitochondrial content, respiration, reactive oxygen species (ROS) production and calcium retention capacity (mCRC). Indices of mitochondrial quality control (MQC), including markers of fusion (MFN1 and 2), fission (Drp1), mitophagy (Parkin) and autophagy (p62 and LC3I and II) were measured using immunoblots. Muscle cross-sections were stained for neural cell adhesion molecule (NCAM, a marker of denervation). HDBR triggered muscle atrophy, decreased mitochondrial content and respiration and increased mitochondrial ROS production. HDBR had no impact on mCRC or MQC markers but increased markers of autophagy and denervation. Exercise prevented the deleterious effects of HDBR on leg muscle volume, mitochondrial ROS production and markers of autophagy and denervation. Exercise also increased mitochondrial content and respiration without altering mCRC and MQC markers. Collectively, our results indicate that an exercise countermeasure that can be performed in bed is effective in protecting muscle and mitochondrial health during HDBR in older adults. KEY POINTS: Conditions associated with muscle unloading, such as immobilization, bed rest or microgravity, result in muscle atrophy and weakness, particularly in older adults. Mitochondrial dysfunctions are thought to contribute to muscle atrophy caused by unloading and ageing. However, whether exercise can counteract the deleterious effects of unloading in older adults remains largely unexplored. Here, we report that older adults exposed to 14 days of head-down tilt bed rest (HDBR) displayed upper leg muscle atrophy, a decrease in mitochondrial content and respiration, an increase in HO emission, and an increase in autophagy and denervation markers. No impact of HDBR on mitochondrial quality control was observed. A multimodal exercise countermeasure prevented the deleterious effects of HDBR on upper leg muscle volume, mitochondrial reactive oxygen species emission, and markers of autophagy and denervation and increased mitochondrial content and respiration. These findings highlight the effectiveness of exercise in promoting muscle and mitochondrial health in older adults undergoing bed rest.
线粒体功能障碍被认为会导致肌肉萎缩和无力，这在衰老过程以及因固定、卧床休息和微重力引起的机械性负荷减少期间会出现。老年人在因负荷减少而出现肌肉和线粒体功能障碍方面风险更高。尽管众所周知运动可促进肌肉和线粒体健康，但运动对老年人机械性负荷减少期间的保护作用在很大程度上仍未得到探索。在此，我们研究了14天头低位卧床休息（HDBR）对55至65岁老年男性和女性的影响，其中一组有多模式运动对策，另一组没有。使用磁共振成像评估腿部肌肉体积。对股外侧肌进行活检以评估线粒体含量、呼吸、活性氧（ROS）产生和钙保留能力（mCRC）的标志物。使用免疫印迹法测量线粒体质量控制（MQC）指标，包括融合标志物（MFN1和2）、裂变标志物（Drp1）、线粒体自噬标志物（Parkin）和自噬标志物（p62以及LC3I和II）。对肌肉横截面进行神经细胞黏附分子（NCAM，去神经支配的标志物）染色。HDBR引发了肌肉萎缩，降低了线粒体含量和呼吸，并增加了线粒体ROS产生。HDBR对mCRC或MQC标志物没有影响，但增加了自噬和去神经支配的标志物。运动预防了HDBR对腿部肌肉体积、线粒体ROS产生以及自噬和去神经支配标志物的有害影响。运动还增加了线粒体含量和呼吸，而未改变mCRC和MQC标志物。总体而言，我们的结果表明，一种可在床上进行的运动对策在保护老年人HDBR期间的肌肉和线粒体健康方面是有效的。要点：与肌肉负荷减少相关的情况，如固定、卧床休息或微重力，会导致肌肉萎缩和无力，尤其是在老年人中。线粒体功能障碍被认为会导致因负荷减少和衰老引起的肌肉萎缩。然而，运动是否能抵消老年人负荷减少的有害影响在很大程度上仍未得到探索。在此，我们报告，经历14天头低位卧床休息（HDBR）的老年人出现了大腿肌肉萎缩、线粒体含量和呼吸减少、HO释放增加以及自噬和去神经支配标志物增加。未观察到HDBR对线粒体质量控制有影响。一种多模式运动对策预防了HDBR对大腿肌肉体积、线粒体活性氧释放以及自噬和去神经支配标志物的有害影响，并增加了线粒体含量和呼吸。这些发现突出了运动在促进卧床休息的老年人肌肉和线粒体健康方面的有效性。
