Age-related changes in glutathione availability and skeletal muscle carbonyl content in healthy rats (original) (raw)
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Free Radical Biology and Medicine, 1999
This study was conducted in order to provide evidence for the role of reactive oxygen species (ROS) in human skeletal muscle aging. We used human muscle samples obtained from hospitalized patients in an open study with matched pairs of individuals of different ages. The subjects, ranging in age from 17 to 91 years, were grouped as follows: 17-25-, 26 -35-, 36 -45-, 46 -55-, 56 -65-, 66 -75-, 76 -85-, and 86 -91-year-old groups. To investigate the relationship between muscle aging and oxidative damage we measured total and Mn-dependent superoxide dismutase (total SOD, MnSOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities; total reduced and oxidized glutathione (GSHtot, GSH, and GSSG) levels; lipid peroxidation (LPO), and protein carbonyl content (PrC). Total SOD activity decreases significantly with age in the 66 -75-year-old group, although MnSOD activity increases significantly in the 76 -85-year-old group. The activity of the two H 2 O 2 detoxifying enzymes (GSHPx and CAT) did not change with age, as do GSHtot and GSH levels. GSSG levels increased significantly (76 -85-and 86 -91-year-old groups) with age. We observed a significant increase in LPO levels (66 -75-and 76 -85-year-old groups), although the PrC content shows a trend of increase without gaining the statistical significance. These results support the idea that ROS play an important role in the human muscle aging process.
Free Radicals and Human Aging Muscle
Systems Biology of Free Radicals and Antioxidants, 2014
Aging is an inevitable biological process, characterized by a general decline in physiological and biochemical functions of the major systems. In the case of the neuromuscular system, reductions in strength and mobility cause a deterioration in motor performance, impaired mobility, and disability. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in accumulation of reactive oxygen species (ROS). As the level of oxidative stress in skeletal muscle increases with age, age process is characterized by an imbalance between an increase in ROS production in the organism and antioxidant defenses as a whole. The goal of this chapter is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account (I) different physiological factors, such as sex, fiber composition, muscle type, and function; (II) biochemical alterations in muscle induced by ROS; and (III) oxidative stress markers related to aged muscle, particularly 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and levels of carbonyl residues such as in Carbonyl Proteins (PC). Finally, we analyze data, present in literature, regarding the beneficial effects of nutrition and physical activity in preventing oxidative damages associated with sarcopenia.
Muscle Disuse: Adaptation of Antioxidant Systems Is Age Dependent
2008
This study investigated the age effect on antioxidant adaptation to muscle disuse. Adult and old rats were randomized into 4 groups: weight bearing (control), 3 days of hind-limb unloading (HU), 7 days of HU, and 14 days of HU. Activities of Cu-Zn superoxide dismutase (SOD), catalase, and glutathione (GSH), as well as GSH peroxidase levels were measured in the soleus.
Glutathione, oxidative stress and aging
AGE, 1996
The free radical theory of aging proposes that the impairment in physiological performance associated with aging is caused by the detrimental effects of oxygen free radicals. This is interesting because it provides us with a theoretical framework to understand aging and because it suggests a rationale for intervention, i.e., antioxidant administration. Thus, the study of antioxidant systems of the cell may be very important in gerontological studies. Glutathione is one of the main nonprotein antioxidants in the cell which, together with its related enzymes, constitute the "glutathione system." The involvement of glutathione in aging has been known since the early seventies. Several studies have reported that reduced glutathione is decreased in cells from old animals, whereas oxidized glutathione tends to be increased. Recent experiments from our laboratory have underscored the importance of cellular compartmentation of glutathione. Mitochondrial glutathione plays a key role in the protection against free radical damage associated with aging. Oxidative damage to mitochondrial DNA is directly related to an oxidation of mitochondrial glutathione. In fact, aging is associated with oxidative damage to proteins, nucleic acids, and lipids. These molecular lesions may be responsible for the low physiological performance of aged cells. Thus, antioxidant supplementation may be a rational way to partially protect against age-associated impairment in performance. Apoptosis, a programmed cell death, is an area of research which has seen an explosive growth. Glutathione is involved in apoptosis: apoptotic cells have lower levels of reduced glutathione, and administration of glutathione precursors prevent, or at least delay, apoptosis. Ageassociated diseases constitute a major concern for researchers involved in aging. Free radicals are involved in many such diseases; for instance, cancer, diabetes or atherosclerosis. The key role of glutathione and other antioxidants in the pathophysiology of aging and age-associated diseases is discussed in this review.
Doria et al. Review - Human aging muscle and oxidative system pathway
Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function).
Relationship between Human Aging Muscle and Oxidative System Pathway
Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function).
Effects of age and caloric restriction on glutathione redox state in mice
Free Radical Biology and Medicine, 2003
The main purpose of this study was to determine whether the aging process in the mouse is associated with a pro-oxidizing shift in the redox state of glutathione and whether restriction of caloric intake, which results in the extension of life span, retards such a shift. Amounts of reduced and oxidized forms of glutathione (GSH and GSSG, respectively) and protein-glutathione mixed disulfides (protein-SSG) were measured in homogenates and mitochondria of liver, kidney, heart, brain, eye, and testis of 4, 10, 22, and 26 month old ad libitum-fed (AL) mice and 22 month old mice fed a diet containing 40% fewer calories than the AL group from the age of 4 months. The concentrations of GSH, GSSG, and protein-SSG vary greatly (∼10-, 30-, and 9-fold, respectively) from one tissue to another. During aging, the ratios of GSH:GSSG in mitochondria and tissue homogenates decreased, primarily due to elevations in GSSG content, while the protein-SSG content increased significantly. Glutathione redox potential in mitochondria became less negative, i.e., more pro-oxidizing, as the animal aged. Caloric restriction (CR) lowered the GSSG and protein-SSG content. Results suggest that the aging process in the mouse is associated with a gradual pro-oxidizing shift in the glutathione redox state and that CR attenuates this shift.
Nutrition, 2010
Objective: Aged muscle is characterized by a defect in the ability of leucine to stimulate protein synthesis. We showed previously that antioxidant supplementation improved the anabolic response to leucine of old muscle and reduced inflammation. The aim of the present study was to determine if the positive effects observed in muscle could be related to an improvement of local muscle oxidative status. Methods: Two groups of 20-mo-old male Wistar rats were supplemented or not with rutin, vitamin E, vitamin A, zinc, and selenium during 7 wk. We measured body weight, food intake, oxidative status in muscle and other tissues, gastrocnemius muscle proteolytic activities, and liver glutathione metabolism. Results: Antioxidant supplementation had no effect on muscle antioxidant capacity, superoxide dismutase activities, and myofibrillar protein carbonyl content and induced an increase in muscle cathepsin activities. In other tissues, antioxidant supplementation increased liver glutathione (reduced plus oxidized glutathione) content, reduced oxidative damage in the liver and spleen (as measured by g-keto-aldehyde content), and reduced heart thiobarbituric acid-reactive substances.
The American Journal of Clinical Nutrition, 2011
Background: Aging is associated with oxidative stress, but underlying mechanisms remain poorly understood. Objective: We tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. Design: Eight elderly and 8 younger subjects received stable-isotope infusions of [ 2 H 2 ]glycine, after which red blood cell (RBC) glutathione synthesis and concentrations, plasma oxidative stress, and markers of oxidant damage (eg, F 2-isoprostanes) were measured. Elderly subjects were restudied after 2 wk of glutathione precursor supplementation. Results: Compared with younger control subjects, elderly subjects had markedly lower RBC concentrations of glycine (486.
2014
Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (2371 years) and older (66 7 2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62 72 years) were included. Exercise increased the venous concentration of GSSG in an intensity-dependent manner in young sedentary subjects, suggesting an exercise-induced increase in ROS formation. In contrast, venous GSSG levels remained unaltered during exercise in the older sedentary and active groups despite a higher skeletal muscle expression of the superoxide-generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects were increased. The potential impairment in exercise-induced ROS formation may be an important mechanism underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity upregulates antioxidant systems, which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG.