Swim exercise in Caenorhabditis elegans extends neuromuscular and gut healthspan, enhances learning ability, and protects against neurodegeneration
Swim exercise in Caenorhabditis elegans extends neuromuscular and gut healthspan, enhances learning ability, and protects against neurodegeneration
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DOI：
10.1073/pnas.1909210116
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发表时间：
2019-11-19
影响因子：
11.1
通讯作者：
Driscoll, Monica
中科院分区：
文献类型：
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作者：
Laranjeiro, Ricardo;Harinath, Girish;Driscoll, Monica
定期体育锻炼是已知促进人类健康衰老的最有效、最容易的干预措施。然而，调节全系统运动益处的分子和细胞机制仍然知之甚少，特别是对于不直接参与训练活动的组织。建立短期遗传模型的运动方案对于破译跨组织运动有益于健康衰老的基本机制至关重要。在这里，我们记录了秀丽隐杆线虫长期游泳运动方案的优化，并证明了它对多种衰老组织的益处，即使运动仅发生在成年期的有限阶段。我们发现，每天多次游泳对于运动适应至关重要，从而改善体壁肌肉的结构基因表达、运动性能和线粒体形态。游泳运动训练可增强整个动物的健康参数，例如线粒体呼吸和中年生存，延长咽部和肠道的功能健康寿命，并通过提高学习能力和防止 tau 病、阿尔茨海默病和亨廷顿病模型中的神经变性来增强神经系统健康。值得注意的是，仅在成年早期进行游泳训练才能带来持久的全身益处，在某些情况下，这种益处在中年时期仍然可以察觉。我们的数据揭示了游泳运动对促进多种线虫组织健康寿命的广泛影响，强调了早期运动经验对影响长期健康的效力，并为利用这种遗传模型的强大优势来解析运动依赖性分子回路奠定了基础，从而为老年人带来全系统的健康益处。
Regular physical exercise is the most efficient and accessible intervention known to promote healthy aging in humans. The molecular and cellular mechanisms that mediate system-wide exercise benefits, however, remain poorly understood, especially as applies to tissues that do not participate directly in training activity. The establishment of exercise protocols for short-lived genetic models will be critical for deciphering fundamental mechanisms of transtissue exercise benefits to healthy aging. Here we document optimization of a long-term swim exercise protocol for Caenorhabditis elegans and we demonstrate its benefits to diverse aging tissues, even if exercise occurs only during a restricted phase of adulthood. We found that multiple daily swim sessions are essential for exercise adaptation, leading to body wall muscle improvements in structural gene expression, locomotory performance, and mitochondrial morphology. Swim exercise training enhances whole-animal health parameters, such as mitochondrial respiration and midlife survival, increases functional healthspan of the pharynx and intestine, and enhances nervous system health by increasing learning ability and protecting against neurodegeneration in models of tauopathy, Alzheimer's disease, and Huntington's disease. Remarkably, swim training only during early adulthood induces long-lasting systemic benefits that in several cases are still detectable well into midlife. Our data reveal the broad impact of swim exercise in promoting extended healthspan of multiple C. elegans tissues, underscore the potency of early exercise experience to influence long-term health, and establish the foundation for exploiting the powerful advantages of this genetic model for the dissection of the exercise-dependent molecular circuitry that confers system-wide health benefits to aging adults.