By Tiffany Chen

As people pass the 30-year-old benchmark, chances are they’re already losing muscle. But a new study published in Nature Metabolism on April 13 found that a nightly jog on the running wheel for old mice reverses aging’s effect on muscle stem cells and regenerates muscle tissue.

“We’ve been very interested for a long time on how a stem cell in a young individual versus an old individual are different. Clearly, the older we get, the less we’re able to repair our tissue from our stem cells,” says correspondent author Thomas Rando of Stanford University, in a lecture presenting early results of the study in 2018. “Are there ways we can intervene in an aged animal to restore youthful functions to these old cells?” 

Researchers know that exercising comes with many benefits in promoting our healthspan, and also slows down muscle aging. Now, the Stanford team suggests that aerobic exercise might reverse the effect of aging by accelerating muscle repair and improving muscle stem cells’ function in old mice. In other words, exercising can restore the old muscle stem cells to a youthful state. 

The team provided one group of young and old mice three weeks of access to running wheels while the other group of mice got locked wheels. The group of exercising young and old mice established a routine, running 10 km (6.2 miles) and 5 km (3.1 miles) per night, respectively. In humans, the level of exercising roughly translates to regular aerobic exercise such as swimming, running, and cycling, according to Rando’s interview with Inverse. 

After three weeks, the team injured the muscles of the mice to compare their ability in muscle repair. Both active and inactive young mice have no problem in repairing muscle damage in their body. However, in older animals, mice that exercised did significantly better in forming new muscles than those that did not. Surprisingly, only older animals saw the benefit of wheel running. 

“The effect in old animals is very significant,” said Rando in a press release published by Stanford Medicine news center. “We found that regular exercise restores youthfulness to tissue repair. Their muscle stem cells start to look and behave like those of much younger animals.”

The researchers also transplanted muscle stem cells from non-active, old mice into injured muscles of young mice and found that the old donor cells performed poorly in repairing muscles. But muscle stem cells from the wheel-running old mice behaved like young stem cells, forming more fibers to repair the tissue. Regular exercise activates the dormant muscle stem cells in aged animals.

However, the benefit of exercise in old muscle stem cells completely vanished two weeks after the animals stopped exercising, suggesting consistent exercise is the key to muscle rejuvenation. 

Instead of producing more muscle stem cells, the aerobic exercise woke the dormant muscle stem cells through a tiny protein named Cyclin D1. The protein decreases in the muscle with age. Restoring Cyclin D1 levels in stem cells to youthful levels presented a Benjamin Button effect in muscles, improving muscle stem cell function and accelerating tissue repair. 

“Exercise truly is restoring youthful properties to the aged stem cells,” said Rando in the 2018 lecture. While there’s no pill for forever-youth yet, researchers may be able to develop drugs that mimic exercise-induced rejuvenation by targeting Cyclin D1 in the future, keeping our aged muscle cells functioning like the young.