Regular low intensity aerobic exercise (aerobic training) provides effective protection against various metabolic disorders. Here, the roles played by transient transcriptome responses to acute exercise and by changes in baseline gene expression during up-regulation of protein content in human skeletalmuscle were investigated after 2 months of aerobic training. Seven untrained males were involved in a 2 month aerobic cycling training program. Mass-spectrometry and RNA sequencing were used to evaluate proteome and transcriptome responses to training and acute exercise. We found that proteins with different functions are regulated differently at the transcriptional level; for example, a training-induced increase in the content of extracellular matrix-related proteins is regulated at the transcriptional level, while an increase in the content of mitochondrial proteins is not. An increase in the skeletal muscle content of several proteins (including mitochondrial proteins) was associated with increased protein stability, which is related to a chaperone-dependent mechanism and/or reduced regulation by proteolysis. These findings increase our understanding of the molecular mechanisms underlying regulation of protein expression in human skeletal muscle subjected to repeated stress (long term aerobic training) and may provide an opportunity to control the expression of specific proteins (e.g., extracellular matrix-related proteins, mitochondrial proteins) through physiological and/or pharmacological approaches.Metabolic syndrome and type 2 diabetes mellitus are among the most widespread diseases in Western countries. Regular low intensity aerobic exercise (aerobic training) improves insulin sensitivity, fat metabolism, and endurance. This effect is associated mainly with a marked increase in skeletal muscle mitochondrial volume/density, increased amounts and activity of mitochondrial enzymes, and increased fat oxidation in muscle both at rest and during low intensity exercise 1-4 . Therefore, investigation of the molecular mechanisms underlying skeletal muscle adaptation to regular aerobic exercise (aerobic training) is of fundamental importance.Acute stress (e.g., each individual exercise session) is associated with transient (over several hours) changes in gene expression in cells; hence, repeated exposure to stress leads to an increase in expression of specific proteins and cellular functions 5,6 . However, regular aerobic exercise is associated not only with a transient transcriptome response after each exercise session, but also with a pronounced change in expression of a large number of genes under baseline conditions 7-9 . Therefore, both repeated responses to acute exercise and changes in baseline gene expression might regulate the tissue content of different proteins. Recent studies examined the role of baseline mRNA levels in regulating proteins in cells [see the review 6 ] and, to a lesser extent, in various human tissues 10-12 . However, to the best of our knowledge, only one study has examined the role of mR...