Elsevier

Ageing Research Reviews

Volume 7, Issue 1, January 2008, Pages 34-42
Ageing Research Reviews

Review
Exercise, oxidative stress and hormesis

https://doi.org/10.1016/j.arr.2007.04.004Get rights and content

Abstract

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 up-regulates 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.

Introduction

The thesis of the hormesis theory is that biological systems respond to the exposure to chemicals, toxins, and radiation with a bell-shaped curve. In toxicology, hormesis is a dose–response phenomenon characterized by a low dose of stimulation, high dose of inhibition, resulting in either a J-shaped or an inverted U-shaped dose–response, which is a non-monotonic response (Calabrese and Baldwin, 2001, Calabrese and Baldwin, 2002, Cook and Calabrese, 2006). Recently, we have extended the hormesis theory to free radical species, which appear to plateau when modulated by aging or physical exercise (Radak et al., 2005) Therefore, we have proposed that exercise modulates free radicals and the effects can be described by the hormesis curve.

The most important effect of exercise on the body is the adaptation process. As any stressor, a single bout of exercise has the capability to induce adaptation, although only in a restricted number of incidences, due to the limited time frame and the characteristics of the loading (Radak et al., 2001c). According to the original stress theory, developed by Selye (1956), for a chronic stressor the body replies with a decreased (alarm reaction), and then with an increased resistance (stage of resistance), which is followed by exhaustion of the body (stage of exhaustion). Therefore, chronic stressors could be very dangerous since the resting period, which is obligatory for recovery and efficient stress response, is missing. Using extremely long-duration exercise as an example, such as 18–24 consecutive hours of running or swimming, even in superbly trained individuals, the body can suffer serious “exhaustion” which could jeopardize the health of the individuals.

On the other hand, under normal conditions, exercise bouts are followed by rest periods and during rest the body has the capability to cope with the exercise “stressor” and as a result, adaptation takes place (Radak et al., 2001c). Indeed, the adaptive effects of regular exercise are systemic and, depending on the characteristics of exercise, the effects are specific. In skeletal muscle, for example, a single bout of long-term aerobic exercise decreases the concentration of glycogen, whereas the normal exercise-induced adaptation to a training regimen is an increase in glycogen concentration which significantly exceeds the level which is found in untrained muscle. Similarly, intensive anaerobic exercise increases the level of lactic acid, which can be as high as 20–25 mmol/l in the blood, but regular anaerobic exercise-associated adaptation enhances the ability to cope with lactic acid by enhancing its elimination.

Regular exercise is carried out for the sole purpose of bringing about adaptation. One of the end points of the exercise-related hormesis curve is physical inactivity, which unfortunately is associated with our modern “civilized” life-style. It is well documented that physical inactivity is associated with increased incidence of a variety of diseases and pathological conditions, including cardiovascular diseases, Type II diabetes, muscular atrophy, Alzheimer's and Parkinson's diseases and obesity (Booth and Lees, 2007).

Interestingly, the beneficial effects of exercise are highlighted according to the human genetic setup, and physical activity has been an important and necessary part of our every day life (Goto and Radak, 2005). Hunting, gathering, fighting and mobility were part of every day life some 100 years ago, and as a result the human genetic pool favors physical activity. Modern life-style, on the other hand, at least in industrialized nations, has essentially eliminated physical activity in the work place. Modern technology and fad diets have resulted in the extensive appearance of life-style-related diseases, which easily can be treated and prevented with regular physical activity (Goto and Radak, 2005, Radak et al., 2004b).

Excessive exercise or overtraining, the other end point of the hormesis curve, increases the risk of disease and jeopardizes health. Indeed, it is also well established that during overtraining the adaptation process fails, and this is primarily due to incomplete recovery from the exercise bouts and, as a result, some maladaptation occurs (Ogonovszky et al., 2005).

Since the present review is limited in length and thus unable to cover the extremely complex systemic adaptation to exercise or fully describe the effects of physical inactivity and overtraining, only some of the most important topics have been selected.

Section snippets

Exercise and fatigue

Regular exercise is an interval stressor. During exercise, metabolic, mechanical and psychological loading result in a wide range of alteration in different organs. During rest, the body recovers, compensates and/or over-compensates the effects of the exercise-stressor. It is a well-known physiological fact that exercise must attain a certain level of stress for adaptation to occur. Indeed, if the exercise-induced stress does not reach this threshold, adaptation will not occur. Low-level

Muscle soreness and muscle hypertrophy

Exercise with unaccustomed loading often results in muscle soreness, which is associated with structural damage to the sarcomeres, disruption of desmin and the myofilament network, splitting of the Z-band and increased intramuscular pressure detected by slit-catheter (Friden et al., 1984, Friden et al., 1986, Friden et al., 1988). This damage activates inflammatory processes, increases DNA binding of NF-κB, activates proteases of the proteasome complex, so that degradation of damaged proteins

Adaptive gene expression in exercise

Two types of physical activity, i.e. resistance exercise and endurance training, cause adaptive responses of gene expression in nuclear and mitochondrial genomes in the skeletal muscle. The changes of gene expression are modulated by a variety of transcription factors constituting the basis of different or common mechanisms of adaptation in the two paradigms. One of the most prominent changes induced by physical activities is upregulation of mitochondrial energy metabolism. The increase

Exercise and the immune system

There is an accumulating body of evidence which suggests that exercise induces considerable alterations to the immune system (Chung et al., 2005). The interaction between exercise-associated stress and the immune system provides an excellent opportunity to study hormesis in this unique condition (Pedersen and Hoffman-Goetz, 2000, Chung et al., 2005). In general, exercise of a high intensity or long duration can cause immunosuppression and increased susceptibility to infection. Indeed, upper

Exercise and free radicals

Exercise can increase the generation of ROS and this is especially true for single bouts of exercise (Alessio and Goldfarb, 1988, Alessio et al., 1988, Davies et al., 1982, Radak et al., 1999b). As a consequence of increased concentration of ROS, oxidative damage of lipids, proteins and DNA have been reported following single bouts of exercise (Alessio et al., 1988, Davies et al., 1982, Gomez-Cabrera et al., 2006, Ikeda et al., 2006, Ji et al., 2006, Mahoney et al., 2005, Paroo et al., 2002,

Exercise and aging

In the present review, we have been discussing the relationship of exercise to the context of hormesis. The link between exercise and aging can also fit the hormesis curve. Generally, during aging, the ability of the body to maintain homeostasis decreases, and regular exercise increases the ability to cope with a variety of stressors. Aging is associated with significant decreases in physical activity, which in turn facilitate the aging process. Aging is a very complex process, which affects

Conclusion

The response of biological systems to stressors can be described by a U-shaped curve. Physical exercise also evokes this hormesis curve-response by the organism. The two end-points of the hormesis curve are inactivity and overtraining, and both of these result in decreased physiological function (Fig. 1). Normal and positively adapted function of the organism can be achieved with regular moderate exercise bouts. The effects of exercise on the immune system, free radicals, muscle function,

Acknowledgement

The present work was supported by Hungarian grants: ETT 38388 awarded to Z. Radák.

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