The Science of Hormesis in Health and Longevity

Suresh Rattan, Marios Kyriazi

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128142547
• Topic: Medicina
• Subtopic: Geriatría

The Science of Hormesis in Health and Longevity provides a comprehensive review of mild stress-induced physiological hormesis and its role in the maintenance and promotion of health. Coverage includes the underlying mechanisms of hormesis, including details of stress-response signaling, an enriched environment, positive challenges and dose-response mechanisms, amongst others. Research from top experts is presented to provide suggestions for developing novel therapeutic strategies, along with lifestyle interventions to promote health and homoeostasis. Researchers in aging and physiology, gerontologists, clinicians and medical students will find this a valuable addition for their work.

• Provides a comprehensive, scholarly review of the current state of hormesis in physiology, health, disease and aging
• Includes multiple perspectives and in-depth analysis by top experts involved in cutting-edge research to provide developing, novel therapeutic strategies, as well as lifestyle interventions
• Offers a clear understanding of hormesis' underlying mechanisms, including details of stress-response signaling, an enriched environment, positive challenges, dose-response mechanisms, and more

Section IV

Hormetic Interventions and Novel Perspectives

Outline

• Chapter 18 Hormesis for Healthy Aging
• Chapter 19 Enhancing Sports Performance Through Ischemic Preconditioning
• Chapter 20 Circadian Regulation of Hormesis for Health and Longevity
• Chapter 21 A Road Map for Cross Operationalization of Resilience
• Chapter 22 Mindfulness, Health, and Longevity
• Chapter 23 Buteyko Breathing Technique and Ketogenic Diet as Potential Hormetins in Nonpharmacological Metabolic Approaches to Health and Longevity
• Chapter 24 Treating Neurodegenerative Diseases With Low Doses of Ionizing Radiation
• Chapter 25 Interactions with Technology as a Cognitive, Healthy Aging Hormetic Stimulus

Chapter 18

Hormesis for Healthy Aging

Suresh I.S. Rattan, Laboratory of Cellular Ageing, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

Abstract

One of the areas where the concept of hormesis has rapidly gained acceptance is in aging research and interventions. Mild stress-induced repeated stimulation of protective mechanisms in cells and organisms has a wide range of health-promoting and life span-extending effects. Moderate and repeated physical exercise is the paradigm for the health beneficial and aging-modulatory effects of hormesis. Molecular mechanisms for the action of hormetins, which bring about the hormesis, comprise a cascade of stress response pathways and stimulation of other pathways of maintenance and repair. Hormetic strengthening of homeodynamics provides wider margins for metabolic fluctuation, stress tolerance, adaptation, and survival of the organism. Hormesis thus counterbalances the progressive shrinkage of the homeodynamic space, which is the major phenotype of aging.

Keywords

Health; stress; homeostasis; homeodynamics; hormetins; stress response

18.1 Introduction

The harmful effects of severe and chronic stress on health and survival have long overshadowed the health-beneficial effects of low level and periodic stress, known as physiological hormesis [1,2]. One of the areas in which hormesis has gained a relatively rapid acceptance is the field of aging research and interventions [3–5]. The main reason for this is the well-documented whole-body-level health-beneficial effects of repeated moderate exercise, which has become the paradigm for physiological hormesis [6,7]. Therefore, biogerontologists started to undertake studies testing the hypothesis that if aging systems are deliberately exposed to repeated bouts of mild stress, this could lead to achieving health-beneficial hormetic effects, including slowing down aging and extending the health span and the life span [8]. Hormesis for healthy aging is, therefore, defined as the life-supporting health-beneficial effects resulting from the cellular responses to single or multiple rounds of mild stress [6,9,10].

This chapter is a review of the published literature on various physical, chemical, and biological conditions which are known to be potentially harmful at high doses, but which at lower doses have the effects of slowing down aging and/or prolonging the life span of cells and organisms. However, it is important to point out that so far only a few studies have been performed with a specific aim to test the applicability hormesis in aging research and interventions. For most other studies, which are interpreted to involve hormesis as the mode of action, those conclusions are generally derived in retrospective analyses [3,7,9].

But first, in order to fully appreciate the rationale for applying hormesis as a modulator of aging and longevity, it may be useful to have a brief overview of the present state of understanding of the phenomenon and process of aging at the biological level.

18.2 Biological Basis of Aging

During the last 50 years, the study of the biological basis of aging, biogerontology, has built a large body of information about the age-related changes in organisms, organs, tissues, cells, and macromolecules. This has also led to working out the molecular mechanisms of aging to a large extent. Based on these developments, certain general principles of aging and longevity are formulated, which can be the basis for translational research and interventions toward achieving a healthy old age. These principles are:

• • Evolutionary principle: According to the evolutionary theories of aging and longevity, aging is an emergent phenomenon seen primarily during the period of survival beyond the natural life span of a species, termed “essential life span” (ELS) [11–14].
• • Nongenetic principle: There is no fixed and rigid genetic program for aging and death of an individual, and there are no gerontogenes whose sole function is to cause aging and to determine the life span of an organism [15–17].
• • Heterogeneity principle: The progression and rate of aging is different in different species, in organisms within a species, in organs and tissues within an organism, in cell types within a tissue, in subcellular compartments within a cell type, and in macromolecules within a cell. Thus, aging is highly heterogeneous at an individual level, and all the way down to the molecules [18].

The above principles of aging and longevity have been inferred from the understanding that the survival of an organism is a dynamic tug between the occurrence of damage and the processes of maintenance and repair systems (MARS). These are also known as the longevity assurance pathways or longevity assurance genes (LAG) [19]. The main examples of MARS are: nuclear and mitochondrial DNA repair; protein repair; antioxidative enzymes; degradation of damaged macromolecules; apoptosis; stress responses (SR); and other higher order MARS including detoxification, wound healing, and the immune system [15,17,20].

All these processes involve numerous genes whose products and their dynamic interactions give rise to a “homeodynamic space,” which is the ultimate determinant of an individual’s chance and ability to survive and maintain a healthy state [15,21]. Three main characteristics of the homeodynamic space are the SR, damage control, and constant remodeling [22,23]. Hundreds of LAG covering a wide range of processes are involved in the stability of the homeodynamic space. However, evolutionary selection processes did not select for these processes to be perfect for infinite survival, but just enough to assure ELS. More importantly, evolution has not developed specific mechanisms for the functional decline and ultimate death of an individual. Aging during the period of survival beyond ELS is a postevolutionary emergent phenomenon. That is why there are no real gerontogenes, but one could call any genes that may appear to influence the rate of aging and the duration of life span as virtual gerontogenes [24].

A progressive shrinkage of the homeodynamic space is the hallmark of aging. This happens owing to the imperfections of MARS, which allow the occurrence and accumulation of molecular damage with a resultant increased heterogeneity [15]. Thus, aging has many facets, and is an emergent, epigenetic, and a metaphenomenon, which is not controlled by any single mechanism. A combination of genes, milieu, and chance determine the course and consequences of aging and the duration of survival of an individual [18].

It is in this framework of the biological basis of aging that applying hormesis for healthy aging makes sense. Intracellular and whole-body-level responses to mild stress can strengthen the homeodynamic space both by slowing down its rate of shrinkage and by recovering the lost space to some extent. Furthermore, the effects of hormesis are cumulative and amplified at the whole-body level even when the initial targets are focused and specific. For example, physical exercise of the leg muscles provides health benefits much beyond the local muscles, and improves metabolic management, immunity, cognition, mood, and so on [6]. Therefore, it is this homeodynamic space as a whole or the individual components of the homeodynamic machinery, which are the targets of hormetic interventions for healthy aging and longevity.

18.3 Hormetics and Hormetins

The scientific study of hormesis is ter...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Section I: History, Terminology and Challenges
• Section II: Clinical and Lifestyle Hormesis
• Section III: Hormetic Stressors
• Section IV: Hormetic Interventions and Novel Perspectives
• Index