“Hormesis” is the theory that regular exposure to small amounts of toxins, or other forms of biological stress have salutary effects, by activating defensive mechanisms. Hormesis is introduced for its possible relevancy as an anti-aging strategy. How increased oxidative stress promotes longevity and metabolic health. Recent evidence suggests that calorie restriction and specifically reduced glucose metabolism induces mitochondrial metabolism to extend lifespan. In conflict with Harman’s free radical theory of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately cause a long-term reduction of oxidative stress.
This type of retrograde response has been named mitochondrial hormesis or mitohormesis, and may, in addition, be applicable to the health-promoting effects of physical exercise in humans and, hypothetically, impaired insulin/IGF-1-signaling in model organisms. Consistently, the abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. The findings indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond.
There is evidence that hormesis is the result of epigenetic adaptations. Recent experimental studies clearly indicate that environmental fluctuations can induce specific and predictable epigenetic-related molecular changes, and support the possibility of the adaptive epigenetic phenomenon. The epigenetic adaptation processes implying alterations of gene expression to buffer the organism against environmental changes support adaptability to the expected life-course conditions. It appears likely that adaptive epigenetic rearrangements can occur not only during early developmental stages but also through the adulthood, and they can cause hormesis, a phenomenon in which adaptive responses to low doses of otherwise harmful conditions improve the functional ability of cells and organisms. In this review, several lines of evidence are presented that epigenetic mechanisms can be involved in hormesis-like responses.