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Aerobic endurance exercise could play an important role in the evolution of home sapiens, oxygen was not important just for survival, but it was crucial to redox mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which, at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1alpha activation could result in decreased oxidative challenge, either by up-regulation of antioxidant enzymes and/or by an increased number of mitochondria that allow lower levels of respiratory activity for the same degree of ATP generation. 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