• Tue. Mar 28th, 2023

Humans are not just large mice: Study identifies science’s muscle-scaling challenge


Mar 16, 2023

In science, findings generated from studying smaller animals usually are generalized and applied to humans, which are orders of magnitude bigger.

A new study from scientists at Northwestern University Feinberg College of Medicine and Shirley Ryan AbilityLab is the initial to show that extrapolating such data to humans primarily based on animal measurements generates incorrect predictions. It also is the initial study to straight measure human muscle contractile properties.

The study was published March 11 in the Journal of Physiology.

The discovery occurred initially when researchers leveraged a distinctive surgical strategy in which a human patient’s gracilis muscle (a massive thigh muscle) was transplanted into the arm to restore elbow flexion immediately after a brachial plexus injury. In the course of action, they have been capable to measure muscle properties and test architectural and scaling predictions straight — a uncommon chance since taking such measurements is very invasive and should happen for the duration of substantial surgery that is becoming performed for other factors. They discovered the gracilis muscle in fact functions as if it has somewhat quick fibers acting in parallel — and not with lengthy fibers, as previously believed primarily based on classic animal anatomical models. Scientists then replicated the benefits all through the course of study.


Human muscle fiber-certain tension is 24% smaller sized than the classic gold typical, as determined from smaller mammals

Especially, they established that human muscle fiber-certain tension is 24% smaller sized than the gold typical that has been employed traditionally, as determined from smaller mammals. Also, they determined that the typical gracilis optimal fiber length is about half of what had been understood to be the case primarily based on detailed anatomical research of muscle tissues from cadavers.

“There’s a cause scientists study animals,” mentioned senior study author Richard L. Lieber, professor of physical medicine and rehabilitation and neuroscience at Feinberg. “Direct measurements of human muscle contractile properties do not happen since they demand muscle tissues to be reduce out of the physique. As a outcome, scientists should study animal muscle tissues and then make predictions as they relate to humans by scaling numbers according to size.”

This study shows, for the initial time, that such extrapolation is basically not precise. The gracilis serves as a great test case since of its simple properties. Since its measurements weren’t accurately predicted, it is probably measurements for all muscle systems are incorrect, according to the researchers.

Initial study to show extrapolating data to humans primarily based on animal measurements generates incorrect predictions.

“When extrapolating from mice to humans, some scaling laws operate beautifully, such as when measuring cardiac output and blood stress,” mentioned Lieber, who also is the chief scientific officer at Shirley Ryan AbilityLab and senior study scientist at the Edward Hines Jr. VA Hospital. “However, by way of this study we’ve demonstrated that the very same scaling principles do not apply in muscle, and are in reality extremely nonlinear. Moving forward, we shouldn’t conduct a mouse muscle study and then basically multiply by physique size to predict human properties.” 

These findings have important implications across disciplines, like surgery, computational musculoskeletal modeling, muscle efficiency and rehabilitation. For instance, predicting how a muscle will carry out immediately after a surgical process is essential. 

Numerous procedures (e.g., tendon lengthening, tendon transfer, surgical release) alter muscle length and force. Nevertheless, at the moment only musculoskeletal models — which are primarily based on indirect measurement solutions and extrapolate animal information to human sizes — can be employed to predict surgical outcomes.

Lieber, for a single, is not deterred by the study findings. 

“Discovering that our anatomical predictions for human muscle are incorrect is large news for human science,” Lieber mentioned. “It is essential that we, as scientists, continually test our assumptions. Now, this expertise sets us on the path to much better fully grasp the efficiency, adaptation and rehabilitation prospective of muscle.”

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