## 4 Implication of Satellite Cells and Myonuclear Accretion
During short-term anabolic steroid treatment, the extra-nuclei acquired were not lost months after treatment arrest whereas muscle size had returned to its basal value [218]. From these results, emerged the \"muscle memory\" theory that differentiates at least two different hypertrophic responses: (i) when adult muscle has no hypertrophic response history, recruitment of new myonuclei is required for de novo muscle hypertrophy, and (ii) when mature muscle has already been submitted to an anabolic stimuli leading to hypertrophy (e.g., resistance training) with a previous increase in the myonuclear number, the addition of new myonuclei seems not needed during a second exposure inducing regrowth [201]. Several studies demonstrated that muscle growth was not necessarily accompanied by an increase in myonuclear number, and, supporting the \"muscle memory\" theory, a pool of extra nuclei was already contained in muscle fibers during regrowth of muscle tissue. Studies giving evidence in favor of this hypothesis included various models of unloading and reloading where myonuclear number remained unchanged [200; 232; 235; 200]. So far, studies failed to provide conclusive results on human skeletal muscle tissue (for review see [236]). Human training and detraining data indicate that myonuclear accrual found during muscle hypertrophy is reverted during detraining with a loss of myonuclei [237]. As suggested by authors [237], the muscle memory of hypertrophic response may be independent of myonuclear number, and probably due to myonuclear DNA methylation, histone modifications, miRNA expression, and other epigenetic mechanisms. As underlined in the study of [PERSON] et al. [48], miR-1 downregulation after a resistance training program remains lower after six months of detraining and could contribute to make a kind of memory induced by a first training adaptation to facilitate regrowth during further exposure. Reinforcing the role of miRNAs in skeletal muscle mass maintenance, it was suggested that miR-21 expression in SCs and muscle could inhibit myogenesis in old mice and contribute to the decline in muscle regeneration during aging [238]. Other miRNAs candidates, such as miR-23a, miR-27a, miR-29b, miR-29c, and others warrant further attention since they are involved in skeletal muscle mass regulation [239; 240; 241; 242]. Finally, chronic resistance exercise also showed modifications in methylation levels of a myriad of genes. Filamin B (FLNB), myosin heavy chain 9 (MYH9), SLIT-ROBO Rho GTPase activating protein 1 (SRGAP1), serglycin (SRGN), Zinc Finger MIZ-type containing 1 (ZMIZ1) genes were found to be hypomethyllated after acute and chronic exercise, and remained hypomethyllated during detraining [52]. Taken together, results showed that SCs activation and myonuclear accretion have an important role during uninjured adult muscle growing and contribute to muscle hypertrophy. Results obtained in mice indicate that factors, such as the type of growth stimulus, its magnitude, and the age of animals directly influence SCs involvement. However, data are still lacking in humans. Concerning exercise modality, resistance training, or high-intensity and damaging endurance exercise seems to be the most effective conditions to solicit SCs. Finally, recent data indicate that epigenetic mechanisms could be involved to facilitate future growth in response to resistance training after a period of detraining. Altogether, these data suggest that the role of SCs, myonuclear accretion, and epigenetics modifications still represent an important challenge for further research in post-developmental muscle growth.