Abstract
Various non-pharmacological practices have been reported to enhance overall health. The molecular effects of exercise have been shown to involve the upregulation of enzymes and transcription factors that enhance antioxidative and anti-inflammatory activity, boost mitochondrial function and growth, and promote a parasympathetic tone. These beneficial changes occur as an adaptive/hormetic response to an initial increase in oxygen radical and nitric oxide production in working muscles. The redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as the key mediator of the cellular defense response. A similar adaptive response appears to occur in response to exposure to heat or cold, hyperbaric or hypobaric oxygen, cupping therapy, acupuncture, caloric restriction, and the consumption of polyphenol-rich plant-based foods or spices, and there is direct or indirect evidence for the involvement of Nrf2. In many cases, additional stress signaling pathways have been observed to be upregulated, including the nicotinamide adenine dinucleotide (NAD+)-sirtuin and the adenosine monophosphate (AMP)-activated protein kinase pathways. We conclude that while several traditional health practices may share a hormetic mechanism-mild radical-induced damage triggers a defense response through upregulation of antioxidative, anti-inflammatory, and repair activities, which may impact body-wide tissue function.