Hormesis in Health and Disease PDF

Preface

There is now a general accordance that some mild stresses have positive effects on the survival, health, aging, and longevity in animal models, particularly in the fly Drosophila melanogaster and nematode Caenorhabditis elegans (reviews in, e.g., Rattan [2008] and Le Bourg [2009]). Studies have also been performed in mammalian models, including human cells in culture, on such hormetic effects, especially with respect to aging and longevity (e.g., Demirovic and Rattan 2013). The idea of using stress to improve health is, at first sight, paradoxical. Indeed, being subjected to stress is not what we usually wish for because, as defined by Selye (1970), "in a strictly medical sense, stress is the rate of wear and tear to which a living being is exposed at any one moment." Furthermore, according to Selye (1975), stress is "a syndrome accompanied by objectively measurable somatic manifestations, and elicited by a variety of emotional and physical agents." This definition does not bear any notion of beneficial and life-supporting effects of stress, and Selye (1975) thus made a distinction between two kinds of stress: "demands for adaptation, experienced as agreeable or beneficial ... are designated as eustress, in opposition to distress."

Later on, Sacher (1977) reviewed the life-prolonging effects of "the class of phenomena in which small quantities of a depressive or toxic agent are stimulatory," that is, stresses with hormetic effects on life span. However, he considered that hormetic effects "are unlikely to occur in the healthy active animal, and are more likely to be significant in the ill or depressed animal," and that "hormesis is in one sense an obstacle in the path of gerontological research, and efforts to understand and annul it would be well justified." In that goal, it was necessary "to breed vigorous animal genotypes and ... to develop living environments that are optimal for their behavioral, physiological, and immunological health" (Sacher 1977). Thus, anyone observing any positive effects of a mild stress on life span could have simply concluded that the results were not of interest and that rearing methods in the lab were probably not optimal.

However, in contrast to Sacher (1977), Frolkis (1993) wrote that "in 1970 we proposed ... that a variety of repeated stress exposures of a mild magnitude trains the defensive mechanisms of the organism ... and may increase the lifespan" and reported a successful experience in rats (see Frolkis [1982], pp. 9, 92). Because Sacher's (1977) article was in English and Frolkis et al. (1976) reported their results in an article written in Russian, it is not surprising that Sacher had a greater impact on biogerontologists for many years and that studying the positive effects of mild stress was then not considered as a top priority.

This was, however, not the end of the story, because during the last decade of the twentieth century, some biogerontologists reported positive effects of mild stress on longevity and stress resistance, mainly in invertebrates (review of these early results in Minois [2000]). After this review was published, many more new results showing that mild stresses can have positive effects on aging and longevity were published, and these positive results, not explained by the use of suboptimal living conditions, revivified the interest in hormesis. Then, the first book on the effects of mild stress on aging was published (Le Bourg and Rattan 2008), quickly followed by a more general book (Mattson and Calabrese 2010) and by a debate among experts on the use of mild stress in human beings (Le Bourg and Rattan 2010). Thus, there was now not only a consensus on the idea that mild stresses can have positive effects on aging, longevity, and resistance to other stresses in model organisms, but also that it could be of use in human beings, even if there was not enough clarity on the precise ways to use mild stress.

Interestingly, studies have been or are being performed on the effects of mild stress in human beings, even if the authors did or do not always interpret their results as hormetic effects. As a matter of fact, it seems that there is a large body of results showing hormetic effects on aging, health, and resistance to severe stresses and diseases in human beings. However, these data are dispersed in the literature and are not always interpreted as hormetic effects, restricting their full apprehension, appreciation, and application. Thus, the paradox is that, even if many authors ignored the existence of hormetic effects, they have gathered results showing such effects. For instance, many studies have shown that moderate and repeated exercise can have positive effects on health and life expectancy (e.g., Paffenbarger et al. 1986), but the authors did not conclude that exercise is a mild stress with hormetic effects.

We thus feel that the time is now ripe to devote an entire book reviewing the evidence for hormesis in humans, as achieved through exercise, radiation, temperature, nutrition, ischemia, fasting, and mental challenge, along with discussing mechanisms of hormesis, and its ethical and legal issues. Our motivation is to convince clinicians, researchers, health-care personnel, the health-care industry, and social and political policy makers to initiate and implement new strategies to learn the strengths and limits of the dual nature of stress, especially with respect to mild stress-induced hormesis in maintaining health, in the prevention of diseases and even as a therapeutic approach for certain diseases. However, we must emphasize that as editors our aim was to gather contributions from top experts who were absolutely free to present their views in whatever way they chose within the framework of the subject. Thus, this book is an attempt to present the current state of research, questions, debates, doubts, and controversies in hormesis and is composed of four sections: history and terminology, evidence for hormesis in human beings, molecular mechanisms of hormesis, and hormesis in risk assessment.