Molecular Mechanisms Mediating Adaptation to Exercise.

Several experimental and human studies documented the preventive and therapeutic effects of exercise on the normal physiological function of different body systems during aging as well as various diseases. Recent studies using cellular and molecular (biochemical, proteomics, and genomics) techniques indicated that exercise modifies intracellular and extracellular signaling and pathways. In addition, in vivo or in vitro experiments, particularly, using knockout and transgenic animals, helped to mimic physiological conditions during and after exercise. According to the findings of these studies, some important signaling pathways modulated by exercise are Ca2+-dependent calcineurin/activated nuclear factor of activated T-cells, mammalian target of rapamycin, myostatin/Smad, and AMP-activated protein kinase regulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha. Such modulations contribute to cell adaptation and remodeling of muscle fiber type in response to exercise. Despite great improvement in this field, there are still several unanswered questions as well as unfixed issues concerning clinical trials' biases and limitations. Nevertheless, designing multicenter standard clinical trials while considering individual variability and the exercise modality and duration will improve the perspective we have on the mechanisms mediating adaptation to exercise and final outcomes.