Maintenance of muscle strength is essential for an individual’s health and well-being. In fact, loss of muscle strength is a prognostic indicator for a variety of disorders including sarcopenia, cancer, and neuromuscular diseases. Decline in muscle strength is also a significant issue for space explorers. Therefore, a major challenge for muscle health research is to understand the genetic mechanisms regulating strength. C. elegans is an established genetic model that has muscle with genetic and physiological similarities to human muscle. Aging C. elegans also show muscle deterioration with age much like humans. Thus, prospective life-long muscle health studies can be accomplished in the roundworm C. elegans.
To make C. elegans a comprehensive genetic model for muscle health investigations, we engineered NemaFlex—a microfluidic device containing deformable pillars for quantifying muscle strength in C. elegans. Animals crawl through the pillar array, causing pillar displacements from which local force data can be extracted. Since the forces fluctuate depending on the animal’s behavior (velocity, body conformation, and position with respect to pillar), reproducible quantitation of animal strength has thus far remained elusive. We establish NemaFlex for high throughput muscle strength assays by developing a robust experimental protocol and analysis workflow to sample the full range of forces and define a metric for maximum strength. We also configure NemaFlex for recording strength across virtually the entire lifespan of animals permitting sarcopenia investigations.
We find that forced contractions, such as induced by an acetylcholine agonist, show the same maximum strength as the untreated animals suggesting NemaFlex quantitates maximum strength. We tested mutants with neuronal defects (unc-17 and unc-119) and impaired sarcomeres (unc-52 and unc-112) and observe changes that verify the neuromuscular origin of strength. We profile strength across the lifespan of a wild-type population, and our results show that strength increases 7-fold from the young adult followed by a sharp late-age decline—providing the first direct evidence of muscle strength loss due to aging, similar to sarcopenia in humans. In summary, NemaFlex is a powerful tool to conduct prospective life-long investigations of muscle strength in C. elegans and mutants.
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