(Press-News.org) CHAMPAIGN, Ill. — New research offers potential good news for those who’ve lapsed at the gym. The study found that mice that voluntarily ran on an exercise wheel for four weeks, stopped for four weeks and ran again for another four weeks saw unexpected gains. The second bout of wheel running led to a bigger increase in the size of muscle fibers than the first, even though the retraining effort was less intense than the initial bout, researchers report.
The findings are detailed in the American Journal of Physiology: Cell Physiology.
“My lab is very interested in understanding whether our body remembers that we’ve exercised before,” said University of Illinois Urbana-Champaign health and kinesiology professor Diego Hernandez-Saavedra, who led the new research with Ph.D. candidate Clay Weidenhamer. “Do we have this sort of memory in our body that keeps us healthier or makes us stronger over time?”
Previous studies have suggested that “muscle memory” is driven by muscle satellite cells, which fuse to existing muscle fibers in response to exercise, allowing the muscles to grow.
“When satellite cells fuse with muscle fibers they add new nuclei, which is why our muscle fibers have multiple nuclei,” Weidenhamer said. Researchers thought that the additional nuclei allowed the muscles to respond more robustly to a second bout of exercise.
But studies looking at whether new nuclei are retained after exercise stops have yielded mixed results.
“There’s not a consensus of whether we keep them or not,” Hernandez-Saavedra said.
In the new study, the team looked at the molecular underpinnings of muscle memory, tracking changes in gene expression at different stages of the experiment. Weidenhamer wanted to focus not only on the immediate effects of training but to also introduce a one-week “washout period” when the mice were not exercising, to avoid capturing any immediate effects. This allowed him to test whether the initial training period somehow primed the muscles in a lasting way.
“During the washout, do the initial adaptations to exercise go away?” Hernandez-Saavedra said. “It turns out that when you exercise the first time and then stop, most of the adaptations seem to go away. But when you have a second bout of exercise, the effects are still there.”
After the second round of exercise, the mice had up to 30% greater muscle mass in their legs than mice that ran on the wheel for only one bout. This increase occurred even though the mice ran only about 6 kilometers per day in the second round of training versus 10 km per day in the first. This suggests that exercise somehow primes the muscles to respond more vigorously to a second round of exercise, even after a pause, Weidenhamer said. But how?
The gene expression analysis offered a clue. It “revealed a robust enhancement” of genes involved in mitochondrial function after the second period of exercise, the researchers wrote. This suggests that the muscle priming comes from the mitochondria, the energy-generating organelles of cells, which kick into gear the next time the animal engages in exercise.
“We didn’t see increases in markers associated with mitochondrial function with the first bout of exercise, even after they stopped exercising, but only after the second bout of exercise,” Hernandez-Saavedra said.
“We gave some of the mice a control diet and others a high-fat diet to induce obesity but saw comparable increases in muscle growth, pointing to an exercise memory that overrides a poor diet,” said Hernandez-Saavedra, who also is a professor of nutritional sciences at Illinois.
In addition to finding that mitochondria play a role in supporting muscle memory, the study reinforces the idea that aerobic exercise also builds muscles, though not to the extent that weight training does, Hernandez-Saavedra said.
“We’re seeing that the intensity of the exercise is enough to cause growth,” he said.
Future studies will follow these dynamics over longer time scales, the researchers said.
“These insights may help identify strategies to preserve muscle health during aging or counteract the effects of a poor diet, opening the door for new interventions against frailty or metabolic disease,” Hernandez-Saavedra said.
The National Institutes of Health and the Muscular Dystrophy Association supported this research.
Editor’s notes:
To reach Diego Hernandez-Saavedra, email dhrnndz2@illinois.edu.
To reach Clay Weidenhamer, email clayw2@illinois.edu.
The paper “Muscle memory of exercise optimizes mitochondrial metabolism to support skeletal muscle growth” is available online.
DOI: 10.1152/ajpcell.00451.2025
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