Hormesis can and Does Work in Humans

Dose-response : a publication of International Hormesis Society, 2012

In contrast to the detrimental action of severe stress conditions, the beneficial effects of mild stress, known as hormesis, is increasingly discussed and studied. A variety of applications for hormesis in risk assessment processes, anti-ageing strategies and clinical therapies have been proposed. The molecular mechanisms underlying the phenomenon of hormesis, however, are not yet fully understood. A possible mechanism that has been proposed for hormesis, the homoeostasis overshoot hypothesis, assumes that an overshoot of repair- and self-recovery mechanisms in response to mild damage can be held responsible for the beneficial effects of hormesis. The present paper proposes 'cellular quality control' as a further explanation of the molecular mechanisms underlying the benefits observed after exposure to mild stress. The most important quality control mechanisms are outlined and their known and hypothesised actions in hormesis are discussed. As an example, different aspects of...

American Journal of Pharmacology and Toxicology, 2008

Hormesis refers to the ability of a chemical or physical agent to condition the physiological state of an organism to tolerate stress with low doses of otherwise harmful agents. Evolutionary evidence shows that the survival and longevity of species hinge on their optimal ability to resist stress challenge. Hormesis is a potent strategy to stimulate latent repair processes to tolerate a specific challenge. Examples of hormetic agent-mimetics, which induce at least partial physiological conditioning, activate known pathways of longevity determinants, i.e., genetic stability, altered metabolism, immunoregulation and stress resistance. Despite the diversity of age-related diseases, glucose and oxidation-mediated protein and DNA damage are common denominators. The associated physiological conditioning-benefits may trigger: 1) activation of latent stress resistance pathways of youthful DNA repair; 2) increased resistance to oxidizing pollutants; 3) improved protein structure and function; 4) improved immunity; 5) damaged tissue remodeling; 6) adjustments in central and peripheral nervous systems; 7) altered metabolism; and 8) delay or breaking of inappropriate protein cross-links. Hormetic mimetics have intervention potential in cancer, diabetes, age-related diseases, infectious diseases, heart and kidney failure, cardiovascular diseases and Alzheimer's disease. Small nucleotide SOS signals, dipeptides, ethanol, thiols, and metals and conserved peptide sequences found in sharks, frogs, woodchucks, and bears, can regulate cytokines, cellular immunity, and central and peripheral neuronal regulatory pathways to promote healthy blood pressure maintenance, heart rate, and metabolic pathways. disease sensitivity. Conserved stress mimetics are highlighted here that rejuvenate DNA and proteins repair and thus may intervene in aging, disease, and trauma. Hibernation Induction Trigger mimetics, Deltorphins, emerge as novel hormetic agents, effective both as pre and post exposure to physiological conditioners to tolerate stress, and prevent damage, and delay possibly aging. Hormesis mimetics offer powerful survival strategies, with better control over the beneficial dose response. Combinations of several mimetics may more closely mimic environmental challenges, which stimulate multiple stress responses.

Ageing Research Reviews, 2008

Physical inactivity leads to increased incidence of a variety of diseases and it can be regarded as one of the end points of the exercise-associated hormesis curve. On the other hand, regular exercise, with moderate intensity and duration, has a wide range of beneficial effects on the body including the fact that it improves cardio-vascular function, partly by a nitric oxide-mediated adaptation, and may reduce the incidence of Alzheimer's disease by enhanced concentration of neurotrophins and by the modulation of redox homeostasis. Mechanical damage-mediated adaptation results in increased muscle mass and increased resistance to stressors. Physical inactivity or strenuous exercise bouts increase the risk of infection, while moderate exercise upregulates the immune system. Single bouts of exercise increases, and regular exercise decreases the oxidative challenge to the body, whereas excessive exercise and overtraining lead to damaging oxidative stress and thus are an indication of the other end point of the hormetic response. Based upon the genetic setup, regular moderate physical exercise/activity provides systemic beneficial effects, including improved physiological function, decreased incidence of disease and a higher quality of life.

Dose-response : a publication of International Hormesis Society, 2009

Journal of Athletic Training

Context: Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-documented physiologic stressors. Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases. Objective: To determine whether whole-body heat stress without exercise triggers cardiovascular, hormonal, and extra-cellular protein responses of exercise. Design: Randomized controlled trial. Setting: University research laboratory. Patients or Other Participants: Twenty-five young, healthy adults (13 men, 12 women; age = 22.1 ± 2.4 years, height = 175.2 ± 11.6 cm, mass = 69.4 ± 14.8 kg, body mass index = 22.6 ± 4.0) volunteered. Intervention(s): Participants sat in a heat stress chamber with heat (73°C) and without heat (26°C) stress for 30 minutes on separate days. We obtained blood samples from a subset of 13 participants (7 men, 6 women) before and after exposure to h...

Dose-response, 2010

ᮀ A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

During normal metabolism, the body produces unstable molecules, the most common of which are the reactive oxygen species (ROS). Increased number of ROS, called oxidative stress, is capable to damage cells. To be able to combat the adverse effects of free radicals, human body triggers the massive production of different antioxidants or accelerates their intake from foods. Scientific studies have demonstrated that long intense exercise such as endurance training, may cause an overwhelming of body's antioxidant defenses, leading to excessive oxidative stress and harmful outcomes. On the other hand regular exercise in intensity and duration has a wide range of beneficial effects on the body, by producing healthy amounts of oxidative stress. Contrary to what is believed until now, oxidative stress is beneficial in small amounts. In fact it's essential, because prompts the body cells to become stronger over time by increasing antioxidants and thus provide protection against potential injury or cellular damage. The beneficial consequences of regular exercise and harmful outcomes of exhaustive exercise due to amount of ROS production fit well with the concept of hormesis. It states that exposure to a low dose of a noxious or toxic agent can bring about results believed beneficial to the long-term welfare of the organisms. According to literature, physical inactivity combined with poor nutrition, excessive smoking and alcohol consumption leads to impairment in physiological functions and reduces the whole body resistance to oxidative stress, and can be regarded as one of the end points of the exercise associated hormesis curve. Moreover, it seems that physical inactivity through molecular pathways could facilitate the incidence of oxidative stress-related diseases. Therefore it seems that the human being is not designed to be inactive for survival.

Dose-Response, 2009

ᮀ Hormesis is a phenomenon in which adaptive responses to low doses of otherwise harmful factors (also called mild stressors) make cells and organisms more robust. Aging is a complex and poorly understood process. This review explores the positive effects of hormesis on aging in animal models and human cell cultures, and discusses whether it might apply to humans. As an example, repeated mild heat stress confers anti-aging benefits to normal human cells in culture. Calorie restriction and xenohormetic compounds such as resveratrol, in large part via activation of sirtuins, decrease risk of common agerelated conditions, such as cancer, cardiovascular disease, type 2 diabetes, and neurological diseases, so lengthening lifespan. Mild stressors and xenohormetic dietary components have diverse molecular targets and affect many pathways. Despite experimental advances in aging research, findings in humans are still quite limited. Moderate-intensity exercise, weight management and healthy diet ameliorate diseases of aging to increase lifespan and this could involve hormesis.

Open …, 2010

The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in a variety of species (including rodents, baboons, turtles, pigs, impalas and chimpanzees), and there are indications that stress exposure alters body temperature in humans. This review aims to assess the translational potential and the different aspects of the body temperature reaction in response to stress. If stress-induced temperature changes are consistent across species, the SIH paradigm may be employed in preclinical and clinical setups and provide a tool to examine the pharmacological, genetic and mechanistic background of stress at both the preclinical and the clinical level.

Dose-Response, 2010

Mimetics of hormetic agents offer a novel approach to adjust dose to minimize the risk of toxic response, and maximize the benefit of induction of at least partial physiological conditioning. Nature selected and preserved those organisms and triggers that promote tolerance to stress. The induced tolerance can serve to resist that challenge and can repair previous age, disease, and trauma damage as well to provide a more youthful response to other stresses. The associated physiological conditioning may include youthful restoration of DNA repair, resistance to oxidizing pollutants, protein structure and function repair, improved immunity, tissue remodeling, adjustments in central and peripheral nervous systems, and altered metabolism. By elucidating common pathways activated by hormetic agent's mimetics, new strategies for intervention in aging, disease, and trauma emerge. Intervention potential in cancer, diabetes, age-related diseases, infectious diseases, cardiovascular disease...