 Recent research suggests that reactive oxygen species, ROS, may function as signaling molecules to promote health and extend lifespan, rather than causing oxidative stress and aging. This concept, known as mitochondrial hormesis or mitohormesis, involves low levels of ROS-inducing an adaptive response in systemic defense mechanisms, including calorie restriction, hypoxia, temperature stress, physical activity, insulin slash IGF-1 receptors, amp-dependent kinase, AMPK, target of rapamycin, TAR, and certuans. Interfering with these ROS signals through pharmacological or natural compounds may have consequences on proteostasis, unfolded protein response, UPR, stem cell maintenance, and stress resistance. Antioxidants, in particular, may be useless or harmful.