## 5 Impact of Exercise Training and Practical Recommendations  
Skeletal muscle mass trends to be attenuated during numerous states, such as disuse atrophy or during aging, and it is well recognized that exercise training minimizes cellular disturbances during such states. Acute exercise decreases protein synthesis according to exercise duration and intensity while mTOR1 pathway is reactivated during recovery [21; 243]. For example, 45 min of running with a progressive increase in velocity for the last 20 min has been shown to decrease puromycin incorporation in several muscles [244], indicating a global decrease of protein synthesis flux during exercise. Interestingly, 10 sessions of resistance exercise interspaced by only 48 h of recovery blunts ERK/MAPK signaling and mTORC1 activation over time [245]. This probably contributes to the attenuation of protein synthesis during repeated bouts of resistance exercise with short recovery [245; 246]. Chronic exercise promotes cellular adaptations leading to improvement of mitochondrial function, reducing oxidative damage and attenuating the rate of skeletal muscle mass decline. A recent study examined the effects of disuse muscle atrophy on mTOR1 activation and muscle protein synthesis during a single bout of resistance training, and whether disuse muscle atrophy could interfere with muscle mass and strength gains after a resistance training protocol [247]. In this work, a 14-day hindlimb suspension decreased basal rRNA level, but not mTORC1 activity and muscle protein synthesis in rats. Importantly, the response of muscle hypertrophy did not differ between the groups [247], showing that disuse muscle atrophy does not alter muscle protein synthesis in response to acute resistance exercise and muscle hypertrophy in response to chronic resistance training. Consistent with these data, another study on disuse atrophy showed that intermittent loading with protein ingestion prevents atrophy during hindlimb unloading probably through mTORC1 signaling pathway [248]. Several factors may impact adaptations to training, such as training backgrounds, nutritional strategies, recovery, exercise modality, exercise volume, and intensity, rest between exercise bouts, genetic/epigenetic factors, age, and environmental conditions [14; 59; 61; 243; 249]. First of all, it is important to note that concurrent exercise (i.e., the incorporation of resistance and endurance training into an exercise program) in untrained individuals promotes generic molecular responses leading to whole muscle adaptations (i.e., increases of aerobic and strength attitudes) and higher gains in muscle mass [250; 251; 252]. However, while endurance-trained subjects present an activation of S6K1 in response to resistance exercise, no effect can be detected in strength-trained individuals [253]. On the contrary, during endurance training, the metabolic sensor AMPK, which is a major inhibitor of mTORC1 pathway [24], can be increased in strength-trained athletes [253]. An investigation in mice showed that whereas a single bout of exercise substantially increases S6K1 and rpS6 phosphorylation, the chronicity of exercise results in a significant attenuation of this response [254]. Interestingly, S6K1 and rpS6 phosphorylation levels were restored after a short detraining period (i.e., 12 days) [254]. Thus, anabolic response seems less sensitive to resistance exercise with chronic exercise and a detraining period may restore mTORC1 pathway response. Another study investigated the involvement of epigenetics mechanisms in response to acute resistance exercise in sedentary and trained men. The authors found that resistance-trained subjects showed hypermethylation of the metabolic genes sterol regulatory element-binding protein (SREBF2) and glycerol-3-phosphate acyltransferase, mitochondrial (GPMA). A lower methylation level of SREBF2 was observed in sedentary subjects [255]. This re sult supports that generic molecular responses and global muscle adaptations occur in sedentary subjects.