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.

Public Health Relevance

A major cause of disability in aged individuals is the loss of motor function or frailty, which in turn leads to morbidity, loss of independence, and reduced quality of life. A new method for studying age-related loss of power and identifying interventions to slow the loss of power in a model system is proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG042690-02
Application #
8661673
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Williams, John
Project Start
2013-05-15
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$74,009
Indirect Cost
$24,009
Name
University of Pennsylvania
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Yuan, Jinzhou; Ko, Hungtang; Raizen, David M et al. (2016) Terrain following and applications: Caenorhabditis elegans swims along the floor using a bump and undulate strategy. J R Soc Interface 13:
Yuan, Jinzhou; Raizen, David M; Bau, Haim H (2015) Propensity of undulatory swimmers, such as worms, to go against the flow. Proc Natl Acad Sci U S A 112:3606-11
Yuan, Jinzhou; Raizen, David M; Bau, Haim H (2015) A hydrodynamic mechanism for attraction of undulatory microswimmers to surfaces (bordertaxis). J R Soc Interface 12:20150227
Yuan, Jinzhou; Zhou, Jessie; Raizen, David M et al. (2015) High-throughput, motility-based sorter for microswimmers such as C. elegans. Lab Chip 15:2790-8
Yuan, Jinzhou; Raizen, David M; Bau, Haim H (2014) Gait synchronization in Caenorhabditis elegans. Proc Natl Acad Sci U S A 111:6865-70