Major signaling pathways triggered and/or affected by ROS in skeletal muscle. Low levels of ROS activate specific key signaling molecules such as PGC-1α, AMPK, and MAPK, which control cellular mechanisms for muscle adaptation (oxidative metabolism, mitochondrial biogenesis, and mitochondrial functionality) as well as antioxidant enzymes that function as backregulators of intracellular ROS levels. Slight ROS accumulation also inhibits PPases and promotes the phosphorylation state of many proteins involved in the muscle signaling responses. Moreover, low levels of ROS play an important role in inducing upregulation of growth factors such as IGF-1, which has beneficial effects in muscle protein balance, supports oxidative metabolism, and contributes to the development of an oxidant-resistant phenotype, therefore preventing oxidative damage and chronic diseases. Thus, low levels of ROS elicit positive effects on physiological muscle responses. By contrast high levels of ROS cause functional oxidative damages of proteins, lipids, nucleic acids and cell components, induce a significant rise of intracellular [Ca²⁺], and promote signaling cascades for apoptosis or autophagy via NF-κB or FoxO paths. For these reasons high ROS levels are reputed to act as etiological, or at least exacerbating factors in muscle atrophy, sarcopenia, wasting, and chronic-/aging-related muscle diseases and myopathies. Depending on their level/persistence, ROS may also turn the same process from “physiologic” into “pathologic”, as in the case of inflammation.