Abstract
Investigating repeated resistance training separated by a training break enables exploration of the potential for a proteomic memory of skeletal muscle growth. Our aim was to examine skeletal muscle proteome response to 10-week resistance training (RT1) followed by 10-week training cessation (i.e. detraining, DT), and finally, 10-week retraining (RT2). Thirty healthy, untrained participants conducted either periodic RT (RT1-DT-RT2, n=17) or a 10-week no-training control period (n=13) followed by 20 weeks of RT (n=11). RT included twice-weekly supervised whole-body RT sessions, and resting vastus lateralis biopsies were obtained every ten weeks for proteomics analysis using high-end DIA-PASEF’s mass spectrometry. The first RT period altered 150 proteins (93% increased) involved in e.g. energy metabolism and protein processing compared with minor changes during the no-training control period. The proteome adaptations were similar after the second RT compared to baseline demonstrating reproducibility in proteome adaptations to RT. Many of the proteins were reversed towards baseline after detraining and increased again after retraining. These reversible proteins were especially involved in aerobic energy metabolism. Interestingly, several proteins remain elevated after detraining, including carbonyl reductase 1 (CBR1) and many proteins involved in muscle contraction or cytoskeleton and calcium-binding. Amongst the latter, calcium-activated protease Calpain-2 (CAPN2) has been recently identified as an epigenetic muscle memory gene. We show that resistance training evokes retained protein levels even after 2.5 months of no training. This is the first study to demonstrate a proteomic memory of muscle growth following resistance training in human skeletal muscle.
Key points
Repeated resistance training in humans separated by a training break (i.e. detraining) enables the identification of temporal protein signatures over the training, detraining, and retraining periods as well as studying reproducibility of protein changes to resistance training.
Muscle proteome adaptations were similar after a second period of resistance training when compared to baseline, demonstrating reproducibility in proteome adaptations to earlier resistance training.
Many of the proteins were reversed towards baseline after detraining and increased again after retraining. These reversible proteins were especially involved in aerobic energy metabolism.
Several proteins remain elevated after detraining, including carbonyl reductase 1 (CBR1) and calcium-binding proteins such as Calpain-2 (CAPN2), a recently identified epigenetic muscle memory gene.
Human skeletal muscle experiences retained protein changes following resistance training persisting over two months demonstrating a potential proteomic memory of muscle growth following resistance training.
Human skeletal muscle proteome response was investigated after 10-week resistance training (RT1) followed by 10-week training cessation (i.e. detraining, DT), and finally, 10-week retraining (RT2). Many of the proteins were reversed towards baseline after DT and increased again after RT2. These reversible proteins were especially involved in aerobic energy metabolism. However, several RT-induced proteins remain elevated after DT, including carbonyl reductase 1 (CBR1) and many proteins involved in muscle contraction or cytoskeleton and calcium-binding. Amongst the latter, calcium-activated protease calpain-2 (CAPN2) is a recently identified epigenetic muscle memory gene. This study shows that resistance training evokes retained protein levels even after 2.5 months of no training and demonstrates a proteomic memory of muscle growth following resistance training in human skeletal muscle. Created in BioRender.com.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The article has been revised to a journal. We have changed some figures to contain individual data points (Fig 6B, Fig 7B, and 8B) as recommended by the journal. We have removed the supplementary figures and added most of them to the main figures resulting in a change to the figure numbering. We have revised the Reactome overrepresentation analysis using quantified proteins as a background similarly as was GO-analysis using ShinyGo. None of the main results were changed. Line graphs include SDs not SEs. Also some other minor changes have been made to the figures to make them easier to read. For example, in Fig 3C we now show only the top 40 proteins instead of the top 50 as the previous font size was too small, whilst maintaining a depiction of the most significant changes.
