Hormesis

[8] The biochemical mechanisms by which hormesis works (particularly in applied cases pertaining to behavior and toxins) remain under early laboratory research and are not well understood.

[4] A form of hormesis famous in antiquity was Mithridatism, the practice whereby Mithridates VI of Pontus supposedly made himself immune to a variety of toxins by regular exposure to small doses.

This was coupled with the work of German physician Rudolph Arndt, who studied animals given low doses of drugs, eventually giving rise to the Arndt–Schulz rule.

[8] The term "hormesis" was coined and used for the first time in a scientific paper by Chester M. Southam and J. Ehrlich in 1943 in the journal Phytopathology, volume 33, pp. 517–541.

[9][10] Over 600 substances show a U-shaped dose–response relationship; Calabrese and Baldwin wrote: "One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria [of a U-shaped response indicative of hormesis]"[11] Carbon monoxide is produced in small quantities across phylogenetic kingdoms, where it has essential roles as a neurotransmitter (subcategorized as a gasotransmitter).

[16] 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 discarded as unwanted byproducts of oxidative phosphorylation in mitochondria by the proponents of the free-radical theory of aging promoted by Denham Harman.

This partial inhibition of mTOR (by the hormetic effect of low-dose rapamycin) modulates mTOR–mitochondria cross-talk, thereby demonstrating mitohormesis; and consequently reducing oxidative damage, metabolic dysregulation, and mitochondrial dysfunction, thus slowing cellular aging.

[23][24] In 2012, researchers at UCLA found that tiny amounts (1 mM, or 0.005%) of ethanol doubled the lifespan of Caenorhabditis elegans, a roundworm frequently used in biological studies, that were starved of other nutrients.

In 2010, a paper in the journal Environmental Toxicology & Chemistry showed that low doses of methylmercury, a potent neurotoxic pollutant, improved the hatching rate of mallard eggs.

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.

[30] 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.

[35][36] Some 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.

[40] A 2005 report commissioned by the French National Academy concluded that evidence for hormesis occurring at low doses is sufficient and LNT should be reconsidered as the methodology used to estimate risks from low-level sources of radiation, such as deep geological repositories for nuclear waste.

[41] Hormesis remains largely unknown to the public, requiring a policy change for a possible toxin to consider exposure risk of small doses.