The Effect of Exercise on Frailty in C. elegans

运动对线虫虚弱的影响

• 批准号: 8506009
• 负责人: Haim H Bau
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506009
• 关键词: Adult; Aerobic; Aerobic Exercise; Affect; Age; Aging; Aging-Related Process; Animal Model; Animals; Attenuated; Behavior; Biological Models; Biology of Aging; Caenorhabditis elegans; Device Designs; Devices; Disease; Electrostatics; Environmental Risk Factor; Equilibrium; Exercise; Fatty acid glycerol esters; Frequencies; Future; Gene Expression; Genes; Genetic; Glycogen; Grant; Homeostasis; Human; Individual; Intervention; Lead; Liquid substance; Location; Locomotion; Longevity; Measurement; Measures; Mediating; Methods; Microfluidic Microchips; Microfluidics; Mitochondria; Modeling; Molecular; Morbidity - disease rate; Motion; Motor; Movement; Muscle; Muscle function; Nematoda; Oxygen; Pathway interactions; Physiology; Positioning Attribute; Process; Quality of life; Recording of previous events; Regimen; Research Personnel; Research Project Grants; Resistance; Role; Sensory; Signaling Protein; Skeletal Muscle; Solutions; Swimming; System; Testing; Width; age effect; age related; aged; aqueous; base; biological systems; cost; density; design and construction; disability; drug discovery; electric field; experience; feeding; frailty; gene discovery; genetic analysis; improved; insulin signaling; interest; lithography; motor function improvement; novel; nutrition related genetics; pressure; programs; public health relevance; research study; response; sarcopenia; simulation

DESCRIPTION (provided by applicant): A major cause for age-related debilitation is the loss of motor power, which is partially explained by muscle loss or sarcopenia. Identifying interventions that slow the loss of power or frailty are of high interest because they may lead to reduced morbidity and improved quality of life. The nematode C. elegans is often used as a model biological system to study aging, and has led to fundamental advances in our understanding of the process. The C. elegans body wall muscle is analogous to human skeletal muscle in several respects including aging-associated sarcopenia/frailty. One of the few human interventions proposed to attenuate sarcopenia and improve motor function is exercise. Yet the mechanism of the beneficial effect of exercise is incompletely understood. We propose a method to study the effect of exercise on frailty in C. elegans. We will develop and characterize a kind of nematode infinity pool, and use this device to test the effect of age and exercise regime on nematode propulsive power. The device will consist of a tapered conduit filled with aqueous solution. The conduit will be subjected to pressure-driven flow directed from its narrow end. The nematode will be inserted at the conduit's wide end and stimulated with a weak DC electric field to deliberately swim upstream. The nematode's response to the electrical field (electrotaxis) is sensory and does not involve any electrostatic forces. As the nematode progresses towards the narrowest end of the conduit, the adverse fluid velocity and the corresponding adverse hydrodynamic force acting on the nematode will increase. Eventually, the nematode will arrive at an equilibrium position, at which its propulsive force will balance the viscous drag force. At its equilibrium position, the animal will swim while maintaining a nearly fixed spatial position. The conduit's width at the equilibrium position will correlate with the nematode's propulsive power. The further upstream the nematode progresses, the larger its propulsive power will be. The propulsive power will be quantified with the aid of direct numerical simulations of the flow field around the nematode. By applying the electric field at predetermined frequencies and durations, the exercise of the animal will be controlled. Experiments will be carried out to correlate the propulsive power with the animal's age and exercise regime. The device will be fabricated with soft lithography. Many conduits will be accommodated on a single substrate to enable high throughput studies. In addition to quantifying the nematode's propulsive power as a function of age and exercise regime, our method can be used, in the future, to study the effect on propulsive power of genetic nutritional, pharmacological, or other environmental perturbations.

描述(由申请人提供)：与年龄相关的衰弱的一个主要原因是运动能力的丧失，这部分可以用肌肉损失或骨骼减少来解释。确定减缓能量丧失或虚弱的干预措施非常有意义，因为它们可能导致减少发病率和改善生活质量。线虫经常被用作研究衰老的模型生物系统，并在我们对衰老过程的理解方面取得了根本性的进展。线虫的体壁肌肉在几个方面与人类骨骼肌相似，包括与衰老相关的石棺减少/虚弱。运动是为数不多的能够减轻骨质疏松症和改善运动功能的人类干预措施之一。然而，锻炼有益效果的机制还不完全清楚。我们提出了一种研究运动对线虫脆弱程度影响的方法。我们将开发并表征一种线虫无限长池，并利用该装置来测试年龄和运动方式对线虫推进力的影响。该装置将由一个充满水溶液的锥形导管组成。管道将受到从其狭窄端引导的压力驱动流。线虫将被插入管道的宽端，并被微弱的直流电场刺激，故意游到上游。线虫对电场(趋电性)的反应是感官的，不涉及任何静电力。随着线虫向管道最窄的一端前进，作用在线虫身上的反向流体速度和相应的反向流体动力将增加。最终，线虫会到达一个平衡的位置，在这个位置上，它的推进力将平衡 粘性阻力。在它的平衡位置，动物将游泳，同时保持一个几乎固定的空间位置。管道在平衡位置的宽度将与线虫的推进力相关。线虫越往上游走，它的推进力就越大。推进功率将通过对线虫周围流场的直接数值模拟来量化。通过以预定的频率和持续时间施加电场，动物的运动将被控制。将进行实验，将推进力与动物的年龄和运动制度相关联。该器件将采用软光刻技术制造。许多管道将容纳在一个单一的衬底上，以实现高通量研究。除了量化线虫的推进力作为年龄和锻炼制度的函数，我们的方法还可以在未来用于研究遗传营养、药物或其他环境扰动对推进力的影响。