New study shows a second exercise bout can boost muscle growth in mice
A new study published in the American Journal of Physiology: Cell Physiology reports that mice who voluntarily ran on an exercise wheel for four weeks, paused for four weeks, and then ran again for another four weeks gained more muscle than those who trained only once. The second round produced bigger increases in muscle fiber size, even though the retraining was less intense in daily distance. The findings point to an exciting form of “muscle memory” that primes muscles to respond more vigorously to a second bout of exercise.
In the experiment, the mice ran about 10 kilometers per day during the first four weeks. During the second four weeks, they ran roughly 6 kilometers per day. Despite the lower daily run distance, the second training cycle yielded up to a 30% greater muscle mass in the legs compared with mice that trained only once. This suggests that prior exercise leaves a lasting, priming effect on the muscles that is reactivated by a subsequent training period.
How muscle memory may work: beyond nuclei
For years, scientists have debated how muscles “remember” prior workouts. A leading idea has centered on satellite cells — stem-like cells that fuse with muscle fibers to add nuclei, potentially boosting growth when exercise resumes. However, questions linger about whether those extra nuclei persist after training stops and how they contribute to a new bout of growth.
Lead researcher Diego Hernandez-Saavedra, a professor at the University of Illinois Urbana-Champaign, and colleagues sought to peek beyond nuclei and explore the underlying molecular changes. The team tracked gene expression at different stages, including a one-week washout period when the mice were not exercising. This washout helped distinguish lasting priming from short-term, immediate effects of training.
Their results showed that most adaptations wane after a period of inactivity, but a second bout of exercise leaves a lasting imprint. The gene analysis revealed a robust upregulation of mitochondrial function pathways after the second four-week training period — a signal the researchers believe points to the mitochondria as key players in exercise memory.
Why mitochondria appear central to muscle memory
Mitochondria, the energy factories within cells, ramp up the machinery needed to produce ATP and support muscle contraction. In this study, markers of mitochondrial function did not rise after the first training period, even after the animals stopped exercising, but they did rise after the second bout. This pattern implies that the initial training sets the stage — the mitochondria become primed to respond more vigorously when exercise is resumed, enabling greater muscle growth despite a lighter second training load.
Diet, health status, and the robustness of memory
Hernandez-Saavedra notes another noteworthy finding: even when some mice were fed a high-fat diet to induce obesity, the increases in muscle growth with the second exercise bout were consistent. This suggests that the exercise memory effect can override, to some extent, dietary challenges, reinforcing the potential of physical activity to preserve muscle health across different metabolic contexts.
Implications for humans and aging
While the study was conducted in mice, researchers say the results add to a growing view that aerobic and endurance elements contribute to muscle health — not just weightlifting. The idea that muscles can be primed to respond more efficiently after a break could influence how we design training programs for aging populations, people recovering from inactivity, or those at risk of frailty. If similar mitochondrial-based priming exists in humans, carefully planned retraining could maximize gains even after periods of rest.
As the authors caution, translating findings from mice to people requires further study. Still, the work opens the door to interventions aimed at preserving muscle health during aging and mitigating the metabolic consequences of poor diet.
What’s next for research
The researchers plan to extend their work to longer timescales and explore whether the muscle memory effects endure with repeated training cycles. They also aim to investigate how different types and intensities of exercise interact with diet and aging, with the goal of identifying strategies to maintain muscle health across the lifespan.
Bottom line
The study strengthens the concept of muscle memory by linking a second round of exercise to enhanced mitochondrial function and greater muscle growth in mice. If similar mechanisms exist in humans, targeted retraining schedules could help people regain or preserve muscle more efficiently after breaks, supporting healthier aging and better metabolic health.
