Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, C79
in vivo measurement of the decline in performance of individual muscle twitches with age.
A. Lopez-Rodriguez1, A. Grant1, C. J. Elliott1
1. Biology, University of York, York, United Kingdom.
As muscles age, their contractions become weaker. In order to understand the neuromuscular basis of this decline in performance and its control by diet and/or genetic background, we have constructed an ergometer to measure the output of the jump muscle (tergal depressor of trochanter) of the fruit fly, Drosophila melanogaster (1). The muscle executes a twitch contraction in response to one action potential in its single motoneuron, which can be driven by single stimuli to the descending giant fibre (2). In our ergometer, the movement of the leg is transduced by a flexible optical fibre illuminating a quadrant photodiode. In wildtype flies, the energy output of the jump muscle declines more rapidly than the population size: energy output is reduced to 50% with flies 18 days old, when 80% of the flies are still alive. Only by 26 days have 50% of the flies died (Fig. 1). Although all jump muscles contract in 20 day old flies, by 30 days, 43% of the jump muscles fail to contract. However, other muscles driven by the giant fibre still contract, suggesting failure of the jump motoneuron or its neuromuscular junction. The composition of the diet affects the fly lifespan, with both poor and rich foods reducing the median lifetime (3). We find that enriching the food with yeast, or restricting nutrient availability by mixing the food with agar, both reduce the age at which the 50% of the energy output occurs. Already by day 15, when an average of 13% of the flies have died, the difference in jump performance is significant (ANOVA, F3,61df=11.4, P < 0.001). Drosophila provide an exceptional transgenic toolbox with which to examine aging, including neurodegenerative disease like Parkinson’s disease. A small proportion of Parkinson’s disease patients express mutations of the LRRK2 gene. In transgenic flies in which the kinase domain of dLRRK is inactivated (4) the lifespan at 29 °C is reduced to 54% (Kaplan-Meier test, Log Rank χ2 =98, P <0.001), and jump muscle performance is reduced by 25% throughout the lifespan - ANOVA: significant effect of age (F 3,186df = 13.4, P < 0.001) and genotype (F 2,186df = 20.8, P < 0.001) but no interaction of age with genotype (F 6,186df =1.5, P = 0.16) indicating a uniform loss of muscle output. We conclude that the fly, like the human (5), shows progressive sarcopenia, with loss of contractile ability preceding loss of functional innervation and population mortality. However, our apparatus provides for a medium-throughput assay to record the consequences of dietary or genetic manipulation.
Where applicable, experiments conform with Society ethical requirements