Study Reveals Muscle Memory at the Protein Level

Researchers at the University of Jyväskylä’s Faculty of Sport and Health Sciences have uncovered a potential new explanation for muscle memory—one that goes beyond what we’ve known about genes and muscle nuclei. For the first time, they’ve shown that muscles retain a "memory" of previous resistance training at the protein level, with these effects persisting for over two months after training stops.

While it’s commonly believed that exercise's benefits fade quickly, this study offers reassuring news: the physiological impact of strength training lasts longer than many expect. Even after a break, muscles retain key adaptations that help them bounce back more efficiently when training resumes.

The research team explored the molecular underpinnings of this phenomenon by measuring levels of thousands of different muscle proteins. Their method—proteomics using high-resolution mass spectrometry—allowed them to quantify more than 3,000 muscle proteins at once.

Training Changes Muscle Proteins—And Some Changes Stick

In the study, participants completed ten weeks of resistance training, followed by a ten-week break, and then another ten weeks of training. Throughout this period, the researchers identified two distinct patterns in how muscle proteins changed.

Some proteins responded dynamically to training, returning to baseline during the break and increasing again with retraining. But more notably, a subset of proteins remained altered throughout the entire cycle, including the break. Among them were calcium-binding proteins like calpain-2, whose gene has recently been shown to retain an epigenetic memory of training.

Previous studies have linked muscle memory to changes in gene expression and the number of muscle nuclei. This new research expands that understanding by showing that training can leave lasting traces at the protein level, too.

“Even though muscle size can return to baseline after a long break, the training history is not entirely erased,” said Professor Juha Hulmi, the study’s lead researcher. “We’ve now demonstrated that proteins involved in muscle function retain a memory trace for at least two and a half months. That may explain why retraining often feels easier than starting from scratch.”

This study is part of the broader TraDeRe project, which is supported by the Finnish Research Council and led by Associate Professor Juha Ahtiainen in collaboration with Professor Hulmi.

Source:
Journal reference:

Hulmi, J, J., et al. (2025) Human skeletal muscle possesses both reversible proteomic signatures and a retained proteomic memory after repeated resistance training. The Journal of Physiology. doi.org/10.1113/JP288104

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