Hormesis and Adaptation

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

Dose-Response, 2009

ᮀ The idea of using hormesis for postponing aging and improving human health has been recently discussed in scientific literature. This paper shows that redundancy in renewal capacity, some portion of which become activated and manifested in hormesis effects, may originate as a result of interaction between living organisms and their environment. It is shown that such redundancy may normally exist for organisms in the wild, and not only in domesticated and laboratory animals. Further development of the hormesis idea requires: (i) investigating regularities of response to multiple stimuli; (ii) studying slow-time responses (e.g., physiological adaptation) to repeated stimuli; (iii) studying connection between slow and fast (e.g., developing at the cellular and sub-cellular levels) stress responses; (iv) translating knowledge accumulated in studies of animal model systems to humans; (v) evaluating unrealized potential for improving health and longevity using hormetic mechanisms. The use of mathematical and computer modeling for translating experimental knowledge about hormesis effects to humans, as well as connection between studying hormetic mechanisms and analyses of the age trajectories of physiological and biological indices affecting U-shapes curves of morbidity-mortality risks using longitudinal data on aging, health, and longevity are discussed.

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.

Biogerontology, 2015

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.

Rejuvenation Research, 2010

The process of aging is accompanied by a progressive reduction of biological dynamical sophistication, resulting in an increased probability of dysfunction, illness, and death. This loss of sophistication is inherent in all aging organisms. However, it may be possible to retard the rate of loss of biological complexity by introducing an increased amount of nonlinear, nonmonotonic external stimulation that challenges the organism and forces it to upregulate its biological processes. This can be achieved by exploiting the multiple effects of hormesis, through a wide range of challenges including physical, mental, and biological stress. Hormesis is widely encountered in biological systems, and its effects are also seen in humans. It is possible to use hormetic strategies (both conditioning hormesis and postexposure conditioning hormesis) to enhance the function of repair processes in aging humans and therefore prevent age-related chronic degenerative diseases and prolong healthy lifespan. Such techniques include dietary restriction and calorie restriction mimetics, intermittent fasting, environmental enrichment, cognitive and sense stimulation, sexuality-enhancing strategies, exposure to low or to high temperatures, and other physicochemical challenges. Current research supports the general principle that any type of a hormetic dose-response phenomenon has an effect that does not depend on the type of stressor and that it can affect any biological model. Therefore, novel types of innovative, mild, repeated stress or stimulation that challenge a biological system in a dose-response manner are likely to have an effect that, properly harnessed, can be used to delay, prevent, or reverse age-related changes in humans.

2018

Aging is complex process characterized by numerous changes that take place at different levels of the biological hierarchy. It is presented as an ontogenic issue, the process of growing old and or the sum of all changes, physiological, genetic, molecular, that occur with the passage of time, from fertilization to death. The heterogenecity of the aging phenotype among individuals of the same species and differences in longevity among species underline the contribution of both genetic and environmental factors in shaping the life span. Aging is associated with a tissue degeneration phenotype marked by a loss of tissue regenerative capacity. Ageing is considered to weaken the body’s ability to respond to stress. The ageassociated changes in the ability of tissues to replace lost or damaged cells is partly the cause of many age-related diseases such as Alzheimer’s disease (AD), cardiovascular disease, type II diabetes, and sarcopenia. Long time stress promotes the aging process, which i...

Annals of the New York Academy of Sciences, 2006

The stress syndrome was discovered accidentally by Hans Selye while searching for new hormones in the placenta. 1 After injecting rats with crude preparations, Selye found adrenal enlargements and involution of thymus and lymph nodes, which he thought were specific for a particular hormone. It occurred to Selye that these symptoms might represent a nonspecific response to noxious agents. Indeed, this was found to be the case when he injected rats with diverse agents. Selye defined the stress response as the "general adaptation syndrome." 2,3 According to this theory, the initial reaction to stress is shock, it is followed by a countershock phase, and gradually resistance develops to the stressor. This resistance may turn into exhaustion, however, if the stressor persists, and death may ensue. Both specific and nonspecific resistance develops during stress. 4 In his last scientific book, Selye defined biologic stress as "the non-specific response of the body to any demand made upon it." 5 Beside the transfer of the word "stress" from physics to biology, Selye also coined the words corticosteroids, glucocorticoids, and mineralocorticoids. 6 Nowadays, the concept of stress has invaded most fields of the biologic, medical, and social sciences. Cellular and molecular biology has become interested in the study of the stress response of human, animal, and plant cells, the consensus being that "any environmental factor potentially unfavourable to living organism" is stress. 7 It is also generally agreed that "if the limits of tolerance are exceeded and the adaptive capacity is overworked , the result may be permanent damage or even death." 8 Three phases of the stress response have been defined based on experimental observations: (1) the response phase of alarm reaction with deviation of functional norm, decline of vitality, and excess of catabolic processes over anabolism, (2) the restitution phase or stage of resistance with adaptation processes and repair processes, and (3) either the end phase, that stage of exhaustion or long-term response when stress intensity is too high, leading to overcharge of the adaptation capacity, damage, chronic disb

Canadian Psychology/Psychologie Canadienne, 2005

The impact of stress on age-related physiological capacities (i.e., resilience) is influenced not only by endowed genetic substrate, but also by individual differences, including the frequency of exposure to stress, the nature and intensity of psychological and physiological reactions to stress, and the efficacy of restorative processes that replenish physiological reserves and fortify against future stress (Cacioppo, Hawkley, & Berntson, 2003). This paper outlines a conceptualization of stress that acknowledges human susceptibility and resistance to the stresses of life and considers the net impact of human frailties and strengths on physiological resilience and health during the aging process.

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.