Hormesis is a biphasic dose response with specific quantitative features for the amplitude and width of the stimulation. It is highly generalizable and independent of biological model, endpoint, inducing agent, level of biological organization and mechanism. Hormesis may be induced via a direct stimulation or by overcompensation to a disruption of homeostasis. The induction of hormesis by low-level stressor agents not only rapidly upregulates adaptive processes to repair damage but also protects the adapted system from damage due to a subsequent challenging dose (toxic) within a definable temporal window. The striking consistency of the amplitude of hormetic response suggests that hormesis provides a quantitative description of biological plasticity. Knowledge of hormesis has particular potential biomedical significance with respect to slowing or retarding both normal aging processes and the progression of severe neurological diseases.

Keywords:
Hormesis, Hormetic dose, Biphasic dose, Adaptive response, Preconditioning, Aging, Biological plasticity, Dose response
1.
Southam CM, Ehrlich J: Effect of extract of western red-cedar heartwood on certain wood-decaying fungi in culture. Phytopathology 1943;33:517-524.
2.
Southam CM: A study of the saprogenicity, and factors influencing decay, of certain brown-rot fungi on western redcedar heartwood test blocks. University of Idaho, School of Forestry, Undergraduate Thesis, 1941.
3.
Calabrese EJ, Baldwin LA: Chemical hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol 2000a;19:2-31.
4.
Calabrese EJ, Baldwin LA: The marginalization of hormesis. Hum Exp Toxicol 2000b;19:32-40.
5.
Calabrese EJ, Baldwin LA: Radiation hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol 2000c;19:41-75.
6.
Calabrese EJ, Baldwin LA: Radiation hormesis: the demise of alegitimate hypothesis. Hum Exp Toxicol 2000d;19:76-84.
7.
Calabrese EJ, Baldwin LA: Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis. Hum Exp Toxicol 2000e;19:85-97.
8.
Calabrese EJ, Baldwin LA: The effects of gamma rays on longevity. Biogerontology 2000f;1:309-319.
9.
Calabrese EJ: Toxicology rewrites its history and rethinks its future: giving equal focus to both harmful and beneficial effects. Environ Toxicol Chem 2011;20:2658-2673.
10.
Calabrese EJ: Historical foundations of hormesis. Homeopathy 2015;104:83-89.
11.
Luckey TD: Hormesis with Ionizing Radiation. CRC Press, Boca Raton, 1980.
12.
Stebbing AR: Hormesis - the stimulation of growth by low levels of inhibitors. Sci Total Environ 1982;22:213-234.
13.
Stebbing AR: A theory for growth hormesis. Mut Res 1998;403:249-258.
14.
Szabadi E: A model of two functionally antagonistic receptor populations activated by the same agonist. J Theor Biol 1977;69:101-112.
15.
Calabrese EJ, Blain RB: The hormesis database: the occurrence of hormetic dose responses in the toxicological literature. Reg Toxicol Pharmacol 2011:61:73-81.
16.
Calabrese EJ, Baldwin LA: The frequency of U-shaped dose responses in the toxicological literature. Toxicol Sci 2001;62:330-338.
17.
Calabrese EJ, Baldwin LA: The hormetic dose-response model is more common than the threshold model in toxicology. Toxicol Sci 2003;71:246-250.
18.
Calabrese EJ, Staudenmayer JW, Stanek EJ 3rd, Hoffmann GR: Hormesis outperforms threshold model in National Cancer Institute antitumor drug screening database. Toxicol Sci 2006;94:368-378.
19.
Calabrese EJ, Stanek EJ 3rd, Nascarella MA, Hoffmann GR: Hormesis predicts low dose-responses better than threshold models. Intl J Toxicol 2008;27:369-378.
20.
Calabrese EJ, Hoffmann GR, Stanek EJ 3rd, Nascarella MA: Hormesis in high-throughput screening of antibacterial compounds in E. coli. Hum Exp Toxicol 2010;29:667-677.
21.
Calabrese EJ: Historical blunders: how toxicology got the dose-response relationship half right. Cell Mol Biol 2005;51:643-654.
22.
Calabrese EJ: Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 2008a;27:1451-1474.
23.
Calabrese EJ, Blain R: The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview. Toxicol Appl Pharmacol 2005;202:289-301.
24.
Calabrese EJ: Overcompensation stimulation: a mechanism for hormetic effects. Crit Rev Toxicol 2000;31:425-470.
25.
Calabrese EJ, Mattson MP: Hormesis provides a generalized quantitative estimate of biological plasticity. J Cell Comm Signal 2011;5:25-38.
26.
Calabrese EJ: Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features. Environ Poll 2013a;182:452-460.
27.
Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, et al: Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol 2007;222:122-128.
28.
Calabrese EJ: Hormetic mechanisms. Crit Rev Toxicol 2013b;43:580-606.
29.
Calabrese EJ, Baldwin LA: Hormesis and high risk groups. Reg Toxicol Pharmacol 2002;35:414-428.
30.
Calabrese EJ: Neuroscience and hormesis: overview and general findings. Crit Rev Toxicol 2008b;38:249-252.
31.
Calabrese EJ: Dose-response features of neuroprotective agents: an integrative summary. Crit Rev Toxicol 2008c;38:253-348.
32.
Calabrese EJ: Hormesis and medicine. Brit J Clin Pharmcol 2008d;66:594-617.
33.
Davey WP: The effect of X-rays on the length of life of Tribolium confusum. J Exp Zool 1917;22:573-592.
34.
Davey WP: Prolongation of life of Tribolium confusum apparently due to small doses of X-rays. J Exp Zool 1919;28:447-458.
35.
Cork JM: Gamma radiation and longevity of the flour beetle. Rad Res 1957;7:551-557.
36.
Calabrese EJ: Low doses of radiation can enhance insect lifespans. Biogerontology 2013c;14:365-381.
37.
Caratero A, Courtade M, Bonnet L, Planel H, Caratero C: Effect of a continuous gamma irradiation at a very low dose on the life span of mice. Gerontology 1998;44:272-276.
38.
Lacoste-Collin L, Jozan S, Cances-Lauwers V, Pipy B, Gasset G, Caratero C, Courtade-Saidi M: Effect of continuous irradiation with a very low dose of gamma rays on life span and the immune system in SJL mice prone to B-cell lymphoma. Rad Res 2007;168:725-732.
39.
Nomura T, Sakai K, Ogata H, Magae J: Prolongation of life span in the accelerated aging Klotho mouse model, by low-dose-rate continuous γ irradiation. Rad Res 2013;179:717-724.
40.
Shin SC, Kang YM, Kim HS: Life span and thymic lymphoma incidence in high- and low-dose-rate irradiated AKR/J mice and commonly expressed genes. Rad Res 2010;174:341-346.
41.
Ristow M, Schmeisser K: Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 2014;12:288-341.
42.
Thorin-Trescases N, Thorin E: Vascular aging and oxidative stress: hormesis and adaptive cellular pathways; in Bondy S, Maiese K (eds): Aging and Age-Related Disorder. New York, Humana Press Inc., 2010.
43.
Son TG, Camandola S, Mattson MP: Hormetic dietary phytochemicals. Neuromol Med 2008;10:236-246.
44.
Arumugam TV, Gleichmann M, Tang SC, Mattson MP: Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res Rev 2006;5:165-178.
45.
Rattan SI: Testing the hormetic nature of homeopathic interventions through stress response pathways. Hum Exp Toxicol 2010;29:551-554.
46.
Rattan SI: Rationale and methods of discovering hormetins as drugs for healthy ageing. Exp Opin Drug Discov 2012;5:439-448.
47.
Mattson MP: What doesn't kill you… Sci Am 2015;313:40-45.
48.
Abete P, Ferrara N, Cioppa A, Ferrara P, Bianco S, Calabrese C, Cacciatore F, Longobardi G, Rengo F: Preconditioning does not prevent post-ischemic dysfunction in aging heart. J Am Coll Cardiol 1996;27:1777-1786.
49.
Van den Munckhof I, Riksen N, Seeger JP, Schreuder TH, Borm GF, Eijsvogels TM, Hopman MT, Rongen GA, Thijssen DH: Aging attenuates the protective effect of ischemic preconditioning against endothelial ischemia-reperfusion injury in humans. Am J Physiol Heart Circ Physiol 2013;304:H1727-H1732.
50.
Krenz M, Baines C, Kalogeris T, Korthuis RJ: Cell survival programs and ischemia/reperfusion. Hormesis, preconditioning, and cardioprotection; in Granger DN, Granger J (eds): Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease, Lecture #44. Digital Library, Morgan and Claypool Life Sciences 2013.
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2015
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