What Marathoner Mice Can Teach Us

If someone left a treadmill in your living room, how far would you run every day just because you felt like you had some energy to burn? Five miles? Zero miles, and you'd use it as a tie rack? How about 65 miles?

Researchers at the University of Pennsylvania and elsewhere studied mutant mice that were missing a particular gene involved in cell signaling. They thought the gene had something to do with muscle development, and sure enough, they found that these mice had some pretty definite abnormalities in their muscles. For example, when an exercise wheel was put in their cages, the mice ran and ran. The wheels were rigged to devices that counted the number of spins they took, and the researchers converted that number to a distance. They found that during just one night (the active period for mice), mutant mice ran an average of 5.4 kilometers on their wheels.

(5K is a much longer haul for a mouse than a human. How much longer? A very rudimentary calculation* tells me that the distance run by the mutant mice each night is roughly proportional to 65 miles for a human. That's not to say that the effort expended would be proportional--I'm no expert on the mechanics of mouse locomotion, and having four legs probably changes things. But that's about how far the same number of strides would take us.)

Even when they weren't on their exercise wheels, the mutant mice were more active, constantly scurrying around their cages. To find out what let the mice stay so active, the researchers took muscles** out of their legs and examined them. Muscles are often described as fast-twitch, used for quick bursts of activity, or slow-twitch, better suited for aerobic exercise. When the researches contracted the cut-out muscles electrically, muscles that should have been fast-twitch fatigued more slowly than usual. Under a microscope, those same muscles contained more muscle fibers and more mitochondria (the cellular powerhouses). Overall, the fast-twitch muscles now looked like slow-twitch ones.

The mutant mice were also skinnier than normal mice, which isn't much of a surprise.

One wonders if these mice, now overly suited for marathoning, were worse at fast-twitch activities such as sprinting or bench-pressing. Sadly, the authors didn't set up any mouse decathlons to find out. But they did look for related genetic variations in humans.

You can't remove a gene from a person like you can from a mouse (at least, ethics boards would probably frown upon it), but you can look for mutations that already exist in human DNA. Conveniently, the gene that was studied in the marathoner mice exists in a few different variants in humans. The researchers looked at DNA from 209 elite athletes in 11 different sports. When broken down by sport, some of the groups displayed distinct genetic profiles. Cyclists, for example, were more likely than usual to have a certain variant of the gene--while triathletes and elite rowers were more likely to have another variant.

In humans, as in mice, the gene in question seems to be involved in how muscles develop. The authors speculate that further research on this gene could help people with muscular diseases, or the obese or elderly. Increasing a person's muscular endurance could help them to lose weight or to keep active in old age. (It could also help professional cyclists cheat, as if they needed any help in that area.)

It's still not clear how a mutant muscle type affects a mouse's or human's motivation to move. The mice in the study weren't put on wheels and forced to run until they collapsed; they voluntarily got up and ran a 5K every night because they felt like it. Maybe this, too, will be a key insight into obesity--the condition of your muscles may not be independent from your desire to exercise. Something at a cellular level told the mice to just keep moving. If we could tap into that force in our own bodies, we might all be able get ourselves off the couch and onto the exercise wheel.

*I converted the distance into strides using this site's measurement of mouse stride length (moving at average speed) and this site's reported stride length for a female marathoner. Better calculations, or ideas about how to compare distances between small four-legged animals and tall bipeds, are welcome.


**Linguistic point of interest: "Muscle" comes from the Latin for "little mouse."

Pistilli, E., Bogdanovich, S., Garton, F., Yang, N., Gulbin, J., Conner, J., Anderson, B., Quinn, L., North, K., Ahima, R., & Khurana, T. (2011). Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles Journal of Clinical Investigation DOI: 10.1172/JCI44945