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一个主要原因是运动能力的丧失，部分原因是肌肉损失或肌少症。确定减缓力量丧失或虚弱的干预措施引起人们高度关注，因为它们可能会降低发病率并提高生活质量。线虫秀丽隐杆线虫经常被用作研究衰老的模型生物系统，并且使我们对这一过程的理解取得了根本性的进展。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/虚弱。运动是为数不多的减轻肌肉减少症和改善运动功能的人类干预措施之一。然而，运动有益作用的机制尚不完全清楚。我们提出了一种研究运动对线虫虚弱影响的方法。我们将开发并表征一种线虫无边泳池，并使用该装置来测试年龄和运动方式对线虫推进力的影响。该装置由一个充满水溶液的锥形导管组成。导管将受到从其窄端引导的压力驱动流的作用。线虫将被插入导管的宽端，并用弱直流电场刺激，使其故意向上游游动。线虫对电场的反应（趋电性）是感觉性的，不涉及任何静电力。当线虫向导管的最窄端前进时，作用于线虫上的不利流体速度和相应的不利水动力将增加。最终，线虫将到达平衡位置，在该位置其推进力将平衡粘性阻力。在其平衡位置，动物会游泳，同时保持几乎固定的空间位置。平衡位置处的导管宽度将与线虫的推进力相关。线虫向上游行进得越远，其推进力就越大。推进力将借助线虫周围流场的直接数值模拟来量化。通过以预定频率和持续时间施加电场，可以控制动物的运动。将进行实验以将推进力与动物的年龄和运动方式相关联。该器件将采用软光刻技术制造。许多导管将被容纳在单个基板上，以实现高通量研究。除了将线虫的推进力作为年龄和运动方式的函数进行量化之外，我们的方法将来还可用于研究遗传营养、药理学或其他环境扰动对推进力的影响。