Hormesis is a term used in biology and pharmacology to describe a beneficial effect of a low dose of a toxin or a stressor. The hormetic response is generally biphasic, with low doses of the stressor having a stimulatory effect and high doses having an inhibitory effect.
"That which does not kill us, makes us stronger."
– Friedrich Nietzsche
Hormesis is derived from the Greek word hórmēsis, meaning “rapid motion” or “to set in motion”. It was first described by a German pharmacologist Hugo Schulz in 1888 when conducting studies on yeast. He noticed that by predisposing the yeast to small amounts of toxic or poisonous substances instead of killing the yeast, actually made the yeast grow faster. In scientific literature, the term hormesis was first used by Southam and Ehrlich in 1943 in an article investigating wood-decaying fungi.
The beneficial stress factor or experience of eustress is also described in the literature as a hormetic stressor. In general, hormesis means the biological effect of some stress-causing factor in the body, where a small quantity is beneficial and strengthens the body, but a high amount is almost toxic. Examples of hormetic stressors include physical training, sunbathing, open-air swimming, plant phytochemicals, and temporary calorie restriction.
Image: Hormesis governs a pleiotropic pro-survival program.
Source: Zimmermann, A. & Bauer, M. & Kroemer, G. & Madeo, F. & Carmona-Gutierrez, D. (2014). When less is more: hormesis against stress and disease. Microbial Cell 1 (5): 150–153.
Hormesis represents a central evolutionary strategy that is limited by individual biological resilience or plasticity. These integrative and adaptive responses share similar quantitative features across species that makes it a key evolutionary factor. Each organism is therefore capable of intelligently defining the degree to which biological performance occurs and on the other end the cost of such enhanced performance in any circumstance or situation.
Responses to hormetic challenges are coordinated across multiple organ systems involving autonomous molecular mechanisms in cells and signals transmitted between different tissues. Exercise and fasting for example force bioenergetic challenges to multiple organ systems, with responses of muscle, liver, neural networks, and adipose tissue which are particularly important during the exercise.
Mechanistically, hormesis seems to be executed by a variety of physiological cellular processes which in cooperation converge on enhanced stress resistance and longevity. Exercise may counteract aging by virtue of a hormetic dose-response relationship: lack of physical activity and overtraining are both disadvantageous, but regular and moderate exercise is beneficial via reactive oxygen species (ROS) mediated preconditioning.
Image: Hormesis and physical exercise.
Source: Pingitore, A. et al. (2015). Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports. Nutrition 31 (7–8): 916–922.
Animal models have shown that hormesis can occur after acute injury or when the onset of a chronic disease has occurred. Examples for this are postinjury metabolic challenges in stroke, myocardial infarction, and traumatic tissue injuries and surgery. Hormetic signals emanating from a tissue under stress can be communicated to distant tissues, a natural phenomenon called “remote conditioning”, which helps the organism survive in stressful and challenging situations.
Image: Examples of metabolic hormesis in the body.
Source: Calabrese, E. & Mattson, M. (2017). How does hormesis impact biology, toxicology, and medicine? NPJ Aging and Mechanisms of Disease 3 (1): 1–8.
The modern Hormesis Theory is based on the 2001 review on the Toxicological Sciences -journal, which explored the effects of nearly 700 different chemicals in the body. The study found that the dose-response curve shows a U- or J-shaped curve, depending on the amount of dose. Small doses were helpful and the higher this dose, the more toxic the substance became. This observation has been confirmed by looking at the dose-response relationship of up to 9,000 different substances.
Hormesis has been neglected in toxicology for nearly 70 years, but in the light of recent studies, hormesis has gained appreciation being a more important factor than value thresholds in explaining the effects of various substances.
Image: Hormetic dose response curve.
Source: Calabrese, V. & Cornelius, C. & Dinkova-Kostova, A. & Calabrese, E. & Mattson, M. (2010). Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxidants & Redox Signaling 13 (11): 1763–1811.
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