Study Says Findings in Mice Cannot Always be Scaled to Humans

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Key points:

  • A new study is the first to show that extrapolating information to humans based on animal measurements generates incorrect predictions.
  • In tests, researchers discovered that human muscle fiber-specific tension is 24% smaller than thought, as determined from small mammals.
  • Moving forward, the study author says researchers shouldn’t conduct mouse muscle studies, and then simply multiply by body size to predict human properties.

When measuring cardiac output and blood pressure, small animal models are incredibly useful, with the information and data scaling well to humans. However, the same can not be said when it comes to muscle performance and rehabilitation.

Now, for the first time, researchers have directly measured human muscle contractile properties, and shown that extrapolating such information to humans based on animal measurements generates incorrect predictions.

For the study, published in the Journal of Physiology, researchers leveraged a unique surgical technique in which a human patient’s gracilis muscle (large thigh muscle) was transplanted into the arm to restore elbow flexion after an injury. In the process, the team was able to measure muscle properties and test architectural and scaling predictions directly—a rare opportunity because taking such measurements is invasive and only done unless surgically necessary. They found that the gracilis muscle actually functions as if it has relatively short fibers acting in parallel—not with long fibers, as previously thought based on traditional animal anatomical models.

Specifically, the team discovered that human muscle fiber-specific tension is 24% smaller than the gold standard that has been used traditionally, as determined from small mammals. Additionally, they determined that the average gracilis optimal fiber length is about half of what had been understood to be the case based on detailed anatomical studies of muscles from cadavers.

Since the measurements for the gracilis muscle weren’t accurately predicted, the researchers believe it’s likely measurements for all muscle systems are incorrect.

“Discovering that our anatomical predictions for human muscle are wrong is big news for human science,” said Richard Lieber, senior study author and chief scientific officer at Shirley Ryan AbilityLab. “It is critical that we, as scientists, continually test our assumptions. Now, this knowledge sets us on the path to better understand the performance, adaptation and rehabilitation potential of muscle.”

 

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