Cellular Mechanism of Muscle Memory

Abstract

It is evident that previously trained muscles reacquire strength and volume at an accelerated rate when re-subjected to resistance training (REXT) even after prolonged detraining. However, specific cellular mechanisms of this phenomenon known as “muscle memory” remain elusive. Because acquired myonuclei have been shown as important biological mediators, and because regulatory genes that control mitochondrial biogenesis are encoded in nuclear genome, we hypothesized, here, that the increased number of nuclei within myofibers would facilitate mitochondrial remodeling and muscle hypertrophy in previously trained muscles during retraining. PURPOSE: To identify a cellular memory mechanism retained in pre-trained muscles and to investigate its effects on structural, functional, and mitochondrial adaptations to retraining preceded by a long-term detraining period. METHODS: Thirty-two SD rats were randomly assigned to 4 groups (n=8 each): Control (C), Pre-training (PT), Training (T), and Retraining (RT). REXT was performed at age of either 8-wk (REXT1) or 36-wk old (REXT2), and were carried out by ladder climbing (1 meter in height) with weights attached to the tail. Each training session consisted of 3 sets of 5 climbing repetitions. Animals were subjected to 2 sessions/day, every third day for 8 wk. The PT and T group performed either REXT1 or REXT2, respectively, where the RT group performed both REXTs 1 and 2. Immunohistochemistry, H&E, COX and SDH staining, and western blot were performed. Comparisons were made using one-way ANOVA followed by a LSD post-hoc test. RESULTS: Body weight was higher in C and PT group compared to T and RT group. DAPI-Pax7 co-staining revealed that myonuclei number was higher (~13%) in PT and RT group compared to C group. Muscle cross-sectional area and muscle weight were greater in RT group compared to T group (p<0.01 for both). COX and SDH activities were significantly greater in RT group compared to T group. PGC-1α protein expression level was greater in RT compared to T group. The expression levels of mitochondrial fusion/fission proteins (i.e. Mfn2, Fis1 and Drp1) were higher in RT group compared to T group (p<0.05). CONCLUSION: Data indicate the acquired myonuclei within a pre-trained muscle fiber as intracellular mediators for the facilitated muscular and mitochondrial adaptations.