The Effect of Exercise on Frailty in C. elegans

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，这部分是由肌肉损失或肌肉减少症解释的。确定能够减缓丧失力量或虚弱的干预措施是非常重要的，因为它们可能导致降低发病率和提高生活质量。秀丽隐杆线虫经常被用作研究衰老的模型生物系统，并导致我们对这一过程的理解取得了根本性的进展。秀丽隐杆线虫的体壁肌肉在几个方面类似于人类的骨骼肌，包括与年龄相关的肌肉减少症/虚弱。提出的为数不多的人类干预措施之一，以减轻肌肉减少症和改善运动功能是运动。然而，运动的有益作用机制尚不完全清楚。我们提出了一种方法来研究运动对秀丽隐杆线虫衰弱的影响。我们将开发并表征一种线虫无限池，并利用该装置测试年龄和运动方式对线虫推进力的影响。该装置将由一个装满水溶液的锥形导管组成。导管将受到来自其狭窄末端的压力驱动流的影响。线虫将被插入导管的宽端，并受到弱直流电场的刺激，故意逆流而上。线虫对电场的反应（趋电性）是感官的，不涉及任何静电力。当线虫向管道最窄端移动时，不利的流体速度和相应的作用在线虫上的不利水动力将会增加。最终，线虫会到达一个平衡位置，在那里它的推进力将平衡

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.