The Effect of Exercise on Frailty in C. elegans

运动对线虫虚弱的影响

基本信息

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
项目类别：
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

项目摘要

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主要原因是运动能力的丧失，这部分由肌肉损失或肌肉减少症解释。确定减缓权力或脆弱性损失的干预措施引起了人们的兴趣，因为它们可能导致发病率降低和生活质量改善。线虫C.秀丽隐杆线虫通常被用作研究衰老的模型生物系统，并导致我们对过程的理解取得了根本的进步。秀丽隐杆线虫体壁肌肉在几个方面类似于人类骨骼肌，包括与衰老相关的肌肉减少症/脆弱。提议减轻肌肉减少症和改善运动功能的少数人干预措施之一就是运动。然而，锻炼有益作用的机制尚不完全理解。我们提出了一种研究练习对秀丽隐杆线虫脆弱的影响的方法。我们将开发并表征一种线虫无边池，并使用此设备来测试年龄和运动状态对线虫推进力的影响。该设备将由装满水溶液的锥形导管组成。该导管将受到从其狭窄端引向的压力驱动流动。线虫将插入导管的宽端，并用弱的直流电场刺激，故意在上游游泳。线虫对电场（电）的反应是感觉的，不涉及任何静电力。随着线虫向导管的最狭窄端的发展，不良流体速度和作用在线虫上的相应的不良流体动力将增加。最终，线虫将达到平衡位置，其推进力将平衡粘性阻力力。在其平衡位置，该动物将在保持几乎固定的空间位置的同时游泳。管道在平衡位置的宽度将与线虫的推进力相关。线虫上游进展越远，其推进力就会越大。推进能力将借助围绕线虫的流场直接数值模拟来量化。通过在预定的频率和持续时间内应用电场，将控制动物的运动。将进行实验，以将推进能力与动物的年龄和运动状态相关联。该设备将用柔软的光刻制成。许多导管将在单个底物上容纳，以实现高通量研究。除了量化线虫的推进能力作为年龄和运动状态的函数外，我们的方法还可以在将来使用对遗传营养，药理或其他环境扰动的推进力的影响。