Past endurance training experience alters skeletal muscle adaptations to re-training in rats

Several studies suggest that skeletal muscle can memorize its past environmental stimuli (e.g. exercise), which alters skeletal muscle adaptations to exercise in later life. For example, increased muscle mass and strength in response to resistance training is faster and greater in previously trained muscles even after a long period of exercise cessation/de-training than in naive muscles. This phenomenon is so-called “muscle memory”. However, limited evidence exists regarding muscle memory related to endurance exercise. Therefore, the aim of this study was to investigate whether past endurance training experience alters skeletal muscle adaptations in response to subsequent endurance re-training. Male Wister rats (8 weeks old) were randomly assigned to four groups: age-matched untrained control (Con), endurance training (ET), de-training (EDT), and re-training (ERT). The training groups were subjected to treadmill running exercise (40 m/min, 60 min/day, 5 days/week) for 6 weeks followed by a de-training period for 6 weeks and a further endurance re-training period for 6 weeks. Approximately 48 h after the last training session, plantaris muscle was removed, and then RNA-sequencing, histochemical, western blot, and chromatin immunoprecipitation analyses were performed. The first 6-week of endurance training did not affect plantaris muscle mass and muscle fiber cross-sectional area (mCSA). However, both plantaris mass and mCSA were significantly higher in ERT than in age-matched Con groups (P < 0.05). The degree of plantaris muscle hypertrophy was also significantly greater in ERT than ET groups (P < 0.05). These results indicated that the 2nd 6-week of endurance training induces plantaris muscle hypertrophy. We also identified 11 muscle hypertrophy-related genes including some heat shock proteins (HSPs), which significantly upregulated in plantaris muscle by acute endurance exercise in our model. The exercise-induced induction of HSP72 and HSP27 was significantly greater in ERT than in ET groups at protein level (P < 0.05). In the present study, we analyzed the distribution of histones at the loci of the 11 target genes. The distribution of histone H3 trimethylation at lysine 27 (H3K27me3), histone H3 trimethylation at lysine 4 (H3K4me3), and histone variant H3.3 was significantly higher in ET, EDT, and ERT groups than in each age-matched Con group (P < 0.05). Furthermore, the exercise-induced upregulation of H3K27me3, H3K4me3, and H3.3 was more drastic in ERT than in ET animals. These results suggested that past endurance training experience would be maintained in rat skeletal muscle via exercise-induced histone modifications. Our findings also suggested that enhanced histone modifications play a key role in promoting skeletal muscle adaptations when muscle faces re-training. JSPS KAKENHI (TS: 23K10584, KM: 20K21749), Kanazawa University “HOZUMINE” project for promotion of research (TS), and Shibuya Science Culture and Sports Foundation (TS, KM). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.