Abraham Z. Reznick

Exercise, Oxidative Damage and Effects of Antioxidant Manipulation

Exercise induces free radical formation in muscle and liver, and oxidative damage, such as lipid peroxidation. The amount of damage depends on exercise intensity, training state and the tissue examined and can be reduced through dietary supplementation of antioxidants such as vitamin E and possibly coenzyme Q10. Supplementation with antioxidants does not increase maximal aerobic capacity or maximal exercise capacity; effects on endurance capacity are unclear. Deficiency of vitamin E or vitamin C greatly reduces endurance capacity, whereas selenium deficiency has no effect on endurance capacity. In studies by the authors, urinary output of the oxidatively damaged RNA base 8-hydroxyguanosine was not affected by several submaximal exercise bouts nor by supplementation with vitamins E and C and beta-carotene in moderately trained humans. In rats, endurance training caused an increase in oxidative damage, as measured by the protein carbonyl concentration of muscle, but not liver. Muscle protein carbonyl concentration returned to normal on detraining. These results indicate that the search for oxidative damage due to exercise and the effects of antioxidant manipulation on such damage should ideally involve examination of several indices of oxidative damage in various tissues after exercise and training.

Characterization of the differentiated antioxidant profile of human saliva.

Saliva is armed with various defense mechanisms, such as the immunological and enzymatic defense systems. In addition, saliva has the ability to protect the mucosa against mechanical insults and to promote its healing via the activity of epidermal growth factor. However, another defense mechanism, the antioxidant system, exists in saliva and seems to be of paramount importance. The most interesting finding of the present study was the demonstration of the existence of much higher concentrations of the various salivary molecular and enzymatic antioxidant parameters in the parotid saliva compared with the submandibular/sublingual saliva. For example, peroxidase, superoxide dismutase, uric acid, and total antioxidant status were higher in resting parotid saliva compared with resting submandibular/sublingual saliva by 2405, 235, 245, and 147%, respectively. Another important finding was the distinction between the salivary antioxidant system and the immunological and enzymatic protective systems, as represented by the salivary concentrations of secretory IgA and lysozyme, respectively. These findings suggest that the profound antioxidant capacity of saliva secreted from parotid glands is related either to the different physiological demands related to eating (parotid predominance), to oral integrity maintenance (submandibular/sublingual predominance), or to the high content of deleterious redox-active transitional metal ions present in parotid saliva. This also may signify that our oral cavity environment is only partially protected against oxidative stress during most of the day and night.

Matrix metalloproteinases and skeletal muscle: A brief review

Matrix metalloproteinases (MMPs) are a family of zinc‐ dependent proteolytic enzymes that function mainly in the extracellular matrix, where they contribute to the development, functioning, and pathology of a wide range of tissues. This mini‐review describes the MMPs and tissue inhibitors of MMPs (TIMPs) in skeletal muscle, and considers their involvement in muscle development, ischemia, myonecrosis, angiogenesis, denervation, exercise‐induced injuries, disuse atrophy, muscle repair and regeneration, and inflammatory myopathies and dystrophies. Despite the very limited information currently available on MMPs and their inhibitors in skeletal muscle, it is becoming increasingly clear that they have important physiological functions in maintenance of the integrity and homeostasis of muscle fibers and of the extracellular matrix. Understanding the roles of MMPs and TIMPs may lead to the development of new drug‐related treatments for various muscle disorders based on suppression or upregulation of their expression. Muscle Nerve 29: 191–197, 2004

Vitamin E inhibits protein oxidation in skeletal muscle of resting and exercised rats

It is well known that exercise induces lipid peroxidation in skeletal muscle and that vitamin E prevents exercise-induced lipid damage. In this study we show for the first time, an increase in protein oxidation in skeletal muscle after a single bout of exercise, related to an exercise-induced decrease in lipophilic antioxidants, and substantial protection against both resting and exercise-induced protein oxidation by supplementation with various isomers (alpha-tocopherol, alpha-tocotrienol) of vitamin E.

TOBACCO-RELATED DISEASES: Is There a Role for Antioxidant Micronutrient Supplementation?

It is clear that smoking causes an increase in free radicals, reactive nitrogen and oxygen species (RNS and ROS, respectively), and that cigarette smoking is associated with increases in the incidence and severity of several diseases including atherosclerosis, cancer, and chronic obstructive lung disease. Although there is still no unequivocal evidence that oxidative stress is a contributor to these diseases or that an increased intake of antioxidant nutrients is beneficial, the observation that smokers have lower circulating levels of some of these nutrients, raises concern. This article discusses the possible links between the observed oxidant-induced damage related to tobacco smoking, effects on cellular mechanisms, and their potential involvement in the causation and enhancement of disease processes.

Networking Antioxidants in the Isolated Rat Heart are Selectively Depleted by Ischemia-Reperfusion

Although cardiac endogenous antioxidants have been reported to be oxidized and decreased by ischemia-reperfusion, little is known whether the changes in these antioxidants are correlated with each other in a systematic relationship. In this study, isolated rat hearts were subjected to various periods of ischemia-reperfusion using the Langendorff method, and the content and/or redox status of tissue antioxidants were analyzed. Significant losses in the tissue hydrophilic antioxidants, ascorbate, and glutathione were observed. These losses were dependent on the duration of the reperfusion period (between 0-40 min) but not of ischemia (20-60 min). Marked increases of dehydroascorbate and glutathione disulfide, the oxidized forms of ascorbate and glutathione, respectively, were found during reperfusion, but these changes were not observed during ischemia. These findings indicate that the tissue hydrophilic antioxidants are easily oxidized and may be the first line of antioxidant defenses during reperfusion. Lipophilic antioxidants, like ubiquinol 9 and vitamin E, were not decreased during ischemia-reperfusion using regular buffer; however, if oxidative stress was induced by addition of H2O2 to the buffer solution during reperfusion after 20 min of ischemia, decreases in both the hydrophilic and hydrophobic antioxidants were noticeable. With 100 microM H2O2, the tissue antioxidant decreases were ubiquinol 9 (39%), vitamin E (3%), glutathione (44%) and ascorbate (58%). Only with 500 microM H2O2 treatment were marked decreases in tissue vitamin E (65%) observed; this was associated with almost complete depletion of tissue ubiquinol 9 (95%). These results suggest that prior to the consumption of vitamin E, other antioxidants are depleted and that vitamin E may serve as the ultimate antioxidant, protecting the integrity of cellular membranes. Thus, in this work, cardiac antioxidants were demonstrated to change in a systematically organized relationship under ischemia-reperfusion. This graded utilization of antioxidants supports the redox based antioxidant network concept, found to be present in other biological systems.

Exercise and immobilization in aging animals: The involvement of oxidative stress and NF-κB activation

In the early 1980s, the concept of threshold of age in exercise and aging was proposed. In several studies it was shown that subjecting young animals to short periods of moderate to intense exercise improved the biochemical and morphological status of their skeletal muscles. This was not the case for old animals subjected to the same exercise regimens. Thus, by measuring several muscle energy-providing enzymes as well as antioxidant enzymes it was demonstrated that their levels and activities increased in young animals postexercise, while in old animals reduced activity of these enzymes was found on completion of the training. However, old animals that started training in young and middle age were still capable of improving their muscle condition as a result of exercise, as long as the onset of training was below a specific age threshold. In the following years, it was shown that intense physical exercise in young humans and animals is accompanied by elevation of oxidative stress parameters in muscles and other organs. Specifically, strenuous training of animals led to increased protein oxidation as measured by protein carbonyl accumulation in muscles, which could be attenuated by the administration of vitamin E. Nuclear factor kappaB (NF-kappaB) is a redox-sensitive transcription factor responsive to closely related reactive oxygen species (ROS) and reactive nitrogen species (RNS) redox cascades. Its involvement in exercise and immobilization has been demonstrated in several studies, indicating that these conditions may lead to inflammatory responses and to oxidative damage to tissues. Indeed, recent studies have revealed that NF-kappaB is involved in inflammatory responses that may result in muscle protein degradation. Additional studies have also demonstrated that the pattern and type of the NF-kappaB activation pathway vary between muscles of young and old animals subjected to limb immobilization for several weeks. This indicates that NF-kappaB may play a crucial role in the regulation of both inflammatory processes and protein turnover and degradation in muscles of old animals. Thus, the modulation of NF-kappaB activity in muscles of old animals by specific inhibitors may provide a means to retard muscle damage and protein degradation under conditions of immobilization.

The Physiology and Biochemistry of Skeletal Muscle Atrophy as a Function of Age

Abstract The skeletal muscles are an important entity in the proper function of aging animals and humans. Studies have shown that until humans are 60-70 years old, age-related changes in muscle function and structure are relatively small, while after 70 years, these alterations are accelerated considerably. Factors responsible for the “aging” of skeletal muscles are complex and include intrinsic biochemical changes in muscle metabolism, changes in the distribution and size of muscle fibers, and a general loss of muscle mass. In addition, other factors like the control of muscle contraction by the motor neural system and the influence of external conditions such as exercise, immobility, nutrition and others may also contribute to the age-related decrease in muscle functions. Studies have shown that with age there is some loss of peripheral motor neurons, reduction in the number of motor units, alterations in the neuromuscular junctions, and selective denervation of Type II muscle fibers. These findings led to the concept of denervation atrophy of skeletal muscles as one of the major mechanisms for muscle degeneration in old age. However, it should be emphasized that the extent of age-related changes varies from muscle to muscle, and some do not seem to be affected by age. For example, it has been shown recently, in animal studies, that weight-bearing muscles are much more susceptible to senescent processes than non-weight-bearing muscles. More work is needed to clarify the contributions of the various factors, especially the role of muscle training in alleviating the symptoms of age-related muscle atrophy.

Muscle Strength and Mass of Lower Extremities in Relation to Functional Abilities in Elderly Adults

Background: Functional and physiological declines in advancing age may be significant limiting factors in reduced physical activity. Sarcopenia of aging, as a normative process or disease, cannot entirely explain reduced physical activity in the elderly. Objective: The purpose of the study was to investigate the relationship between muscle loss and reduction in functional abilities in elderly adults and also to determine whether an exercise program can improve functional performance and muscle quality. Methods: Anthropometric measurements and sensorimotor testing were conducted on 28 volunteers (12 men and 16 women, 82.7 ± 2.4 years of age) who were permanent residents in a skilled nursing facility. Twenty-nine elderly adults (79.3 ± 3.5 years of age) served as a control, nonexercising group. Anthropometric measurements included: weight, height, body fat, and thigh circumference. The muscle strength was tested with a medical isokinetic system. We assessed two sensorimotor functions including a ‘timed up-and-go’ test and a 3-min distance walking test. The institutionalized participants undertook an exercise training program lasting 12 weeks. Results: No significant changes were observed in thigh circumference, body weight, or percentage of body fat in either gender as a result of the exercise training. An improvement in muscle strength was noticed in 82% of the relatively younger group (79–83 years of age) under a slow voluntary contraction at 60°/s (p < 0.05). Post-training results showed a significant improvement in performance in the two sensorimotor tests (p < 0.05). The correlation coefficients between muscle strength and functional ability were weak: r = 0.60 and r = 0.57 for males and females, respectively. Conclusions: This study confirmed the positive effects of an exercise program on functional performance in older adults. The improvement in functional abilities did not correlate with muscle strength, body weight, or body fat.

The Evolutionary Theories of Aging Revisited - A Mini-Review

This short review portrays the evolutionary theories of aging in the light of the existing discoveries from genomic and molecular genetic studies on aging and longevity. At the outset, an historical background for the development of the evolutionary theories of aging is presented through the works of August Weismann (programmed death and the germ plasm theories) including his exceptional theoretical postulation, later experimentally validated by the existence of cell division limits. Afterwards, the theory of mutation accumulation of Peter Medawar and the theory modification by Charlesworth (late-life mortality plateau) are presented as well as the antagonistic pleiotropy hypothesis of George Williams, and the disposable soma theory of Kirkwood and Holliday. These theories are discussed in the light of the different research studies, which include studies on insulin signaling and longevity, the possibility that nuclear factor kappa B may be a major mediator of aging, studies of anti-aging Sirtuins and studies on heat shock proteins and longevity and on gene sets as biomarkers of aging. Finally, the proposals for future research in biogerontology, such as studies on the control of protein synthesis, validation of biomarkers of aging, understanding the biochemistry of longevity and research in the field of gerontologic pathology are presented. Likewise, further attention is suggested regarding the work on telomere shortening, stem cells and studies on understanding the biochemical and molecular basis for longevity in centenarians.