Hormesis

Individuals with low levels of physical activity are at risk for high levels of oxidative stress, as are individuals engaged in highly intensive exercise programs; however individuals engaged in moderately intensive, regular exercise experience lower levels of oxidative stress. High levels of oxidative stress have been linked by some with the increased incidence of a variety of diseases.[6]

It has been claimed that this relationship, characterized by positive effects at an intermediate dose of the stressor (exercise), is characteristic of hormesis.[6] However, it is important to point out that there is evidence that the oxidative stress associated with intensive exercise may have long-term health benefits. This would imply that oxidative stress, itself, provides an example of hormesis (see section on Mitochondrial hormesis), but physical exercise does not.[7]

Alcohol is believed to be hormetic in preventing heart disease and stroke,[8] although the benefits of light drinking may have been exaggerated.[9][10]

In 2012, researchers at UCLA found that tiny amounts (1 mM, or 0.005%) of ethanol doubled the lifespan of Caenorhabditis elegans, a round worm frequently used in biological studies, that were starved of other nutrients. Higher doses of 0.4% provided no longevity benefit.[11] However, worms exposed to 0.005% did not develop normally (their development was arrested). The authors argue that the worms were using ethanol as an alternative energy source in the absence of other nutrition, or had initiated a stress response. They did not test the effect of ethanol on worms fed a normal diet.

In 2010, a paper published in the journal Environmental Toxicology & Chemistry showed that low doses of methylmercury, a potent neurotoxic pollutant, improved the hatching rate of mallard eggs.[12] The author of the study, Gary Heinz, who led the study for the U.S. Geological Survey at the Patuxent Wildlife Research Center in Beltsville, Md., stated that other explanations are possible. For instance, it is possible that the flock he studied might have harbored some low, subclinical infection and that mercury, well known to be antimicrobial, might have killed the infection that otherwise hurt reproduction in the untreated birds.[12]

One of the areas where the concept of hormesis has been explored extensively with respect to its applicability is aging.[13][14] Since the basic survival capacity of any biological system depends on its homeostatic ability, biogerontologists proposed that exposing cells and organisms to mild stress should result in the adaptive or hormetic response with various biological benefits. This idea has now gathered a large body of supportive evidence showing that repetitive mild stress exposure has anti-aging effects.[15][16] Exercise is a paradigm for hormesis in this respect.[16] Some of the mild stresses used for such studies on the application of hormesis in aging research and interventions are heat shock, irradiation, prooxidants, hypergravity, and food restriction.[15][16][17] Some other natural and synthetic molecules, such as celastrols from medicinal herbs and curcumin from the spice turmeric have also been found to have hormetic beneficial effects.[18] Such compounds which bring about their health beneficial effects by stimulating or by modulating stress response pathways in cells have been termed "hormetins".[15] Hormetic interventions have also been proposed at the clinical level,[19] with a variety of stimuli, challenges and stressful actions, that aim to increase the dynamical complexity of the biological systems in humans.[20]

Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), a source of chemical energy. Reactive oxygen species (ROS) have been regarded as unwanted by-products of oxidative phosphorylation in mitochondria by the proponents of the free-radical theory of aging promoted by Denham Harman. The free-radical theory suggests that the use of compounds which inactivate ROS, such as antioxidants, would lead to a reduction of oxidative stress and thereby produce an increase in lifespan.

ROS may perform an essential and potentially lifespan-promoting role as redox signaling molecules which transduce signals from the mitochondrial compartment to other compartments of the cell.[21] Increased formation of ROS within the mitochondria may cause an adaptive reaction which produces increased stress resistance and a long-term reduction of oxidative stress. This kind of reverse effect of the response to ROS stress has been named mitochondrial hormesis or mitohormesis and is hypothesized to be responsible for the respective lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise.[21]

Whether this concept applies to humans remains to be shown, although recent epidemiological findings support the process of mitohormesis, and even suggest that some antioxidant supplements may increase disease prevalence in humans.[22]

Hormesis has been observed in a number of cases in humans and animals exposed to chronic low doses of ionizing radiation. A-bomb survivors who received high doses exhibited shortened lifespan and increased cancer mortality, but at low-dose radiation the ratios of cancer deaths in A-bomb survivors are smaller than those of Japanese averages.[23]

In Taiwan, recycled radiocontaminated steel was inadvertently used in the construction of over 100 apartment buildings causing the long-term (10 years) exposure of 10,000 people. The average dose rate was 50 mSv/year and a subset of the population (1,000 people) received a total dose of over 4,000 mSv over ten years. In the widely used Linear No Threshold (LNT) theory used by regulatory bodies, the expected cancer deaths in this population would have been 302 with 70 caused by the extra ionizing radiation with the remainder caused by natural background radiation. However the observed cancer rate was quite low at 7 cancer deaths when 232 would be predicted by the LNT theory had they not been exposed to the radiation from the building materials. Ionizing radiation hormesis appears to be at work. Described by Professor Charles L. Sanders, Korea Advanced Institute of Science and Technology.[24]

No experiment can be performed in perfect isolation. Thick lead shielding around a chemical dose experiment to rule out the effects of ionizing radiation is built and rigorously controlled for in the laboratory, and certainly not the field. Likewise the same applies for ionizing radiation studies. Ionizing radiation is released when an unstable particle releases radiation, creating two new substances and energy in the form of an electromagnetic wave. The resulting materials are then free to interact with any environmental elements, and the energy released can also be used as a catalyst in further ionizing radiation interactions.[25]

The resulting confusion in the low dose exposure field (radiation and chemical) arise from lack of consideration of this concept as described by Mothersill and Seymory.[26]