ReviewExercise, oxidative stress and hormesis
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.
References (98)
- et al.
Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo
Atherosclerosis
(1999) - et al.
Exercise training enhances endothelial function in young men
J. Am. Coll. Cardiol.
(1999) - et al.
Exercise: a behavioral intervention to enhance brain health and plasticity
Trends Neurosci.
(2002) Intracellular proteolytic systems may function as secondary antioxidant defenses: an hypothesis
J. Free Radic. Biol. Med.
(1986)- et al.
Free radicals and tissue damage produced by exercise
Biochem. Biophys. Res. Commun.
(1982) - et al.
Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle
Free Radic. Biol. Med.
(1999) - et al.
Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral l-arginine supplementation
J. Am. Coll. Cardiol.
(2000) - et al.
Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice
Cell
(2005) - et al.
Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems
J. Nutr. Biochem.
(2005) - et al.
A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin
Ageing Res. Rev.
(2004)
The effect of exercise training on oxidative damage of lipids, proteins, and DNA in rat skeletal muscle: evidence for beneficial outcomes
Free Radic. Biol. Med.
Muscle soreness-induced reduction in force generation is accompanied by increased nitric oxide content and DNA damage in human skeletal muscle
Free Radic. Biol. Med.
Exercise preconditioning against hydrogen peroxide induced oxidative damage in proteins of rat myocardium
Arch. Biochem. Biophys.
Regular exercise improves cognitive function and decreases oxidative damage in rat brain
Neurochem. Int.
Single bout of exercise eliminates the immobilization-induced oxidative stress in rat brain
Neurochem. Int.
Marathon running alters the DNA base excision repair in human skeletal muscle
Life Sci.
The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain
Neurochem. Int.
Exercise, inflammation, and innate immunity
Neurol. Clin.
Adaptive mechanisms to oxidative stress during aging
Mech. Ageing Dev.
Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training
J. Appl. Physiol.
MDA content increases in fast- and slow-twitch skeletal muscle with intensity of exercise in a rat
Am. J. Physiol.
The overtraining syndrome in athletes: a stress-related disorder
J. Endocrinol. Invest.
Effects of eccentric treadmill running on mouse soleus: degeneration/regeneration studied with Myf-5 and MyoD probes
Acta Physiol. Scand.
The unknown mechanism of the overtraining syndrome: clues from depression and psychoneuroimmunology
Sports Med.
Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation
FASEB J.
Involvement of PPAR gamma co-activator-1, nuclear respiratory factors 1 and 2, and PPAR alpha in the adaptive response to endurance exercise
Proc. Nutr. Soc.
Fundamental questions about genes, inactivity, and chronic diseases
Physiol. Genom.
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy
J. Appl. Physiol.
U-shaped dose–responses in biology, toxicology, and public health
Annu. Rev. Public Health
Defining hormesis
Hum. Exp. Toxicol.
Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone
Proc. Natl. Acad. Sci. U.S.A.
Exercise and inflammatory diseases: beneficial effects of exercise as a stimulus of hormesis
Hormesis is biology, not religion
Environ. Health Perspect.
Adaptive response and oxidative stress
Environ. Health Perspect.
VEGF is necessary for exercise-induced adult hippocampal neurogenesis
Eur. J. Neurosci.
Nutrition and cardiovascular mortality
Orv. Hetil.
Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans
J. Appl. Physiol.
Segmental muscle fiber lesions after repetitive eccentric contractions
Cell Tissue Res.
Delayed muscle soreness and cytoskeletal alterations: an immunocytological study in man
Int. J. Sports Med.
Muscle soreness and intramuscular fluid pressure: comparison between eccentric and concentric load
J. Appl. Physiol.
Residual muscular swelling after repetitive eccentric contractions
J. Orthop. Res.
Cellular and molecular aspects of adaptation in skeletal muscle
Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats
J. Physiol.
Oxidative stress in marathon runners: interest of antioxidant supplementation
Br. J. Nutr.
Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress
Circulation
Effect of exercise on coronary endothelial function in patients with coronary artery disease
N. Engl. J. Med.
Does oxidative damage to DNA increase with age?
Proc. Natl. Acad. Sci. U.S.A.
Exercise and upper respiratory tract infections. Is there a relationship?
Sport Med.
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