Redox Homeostasis in Age-Related Muscle Atrophy.

Muscle atrophy and weakness, characterized by loss of lean muscle mass and function, has a significant effect on the independence and quality of life of older people. The cellular mechanisms that drive the age-related decline in neuromuscular integrity and function are multifactorial. Quiescent and contracting skeletal muscle can endogenously generate reactive oxygen and nitrogen species (RONS) from various cellular sites. Excessive RONS can potentially cause oxidative damage and disruption of cellular signaling pathways contributing to the initiation and progression of age-related muscle atrophy. Altered redox homeostasis and modulation of intracellular signal transduction processes have been proposed as an underlying mechanism of sarcopenia. This chapter summarizes the current evidence that has associated disrupted redox homeostasis and muscle atrophy as a result of skeletal muscle inactivity and aging.

Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease.

Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.

Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 µM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice.

Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1(-/-) mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1(-/-) mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1(-/-) mice). SynTgSod1(-/-) mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1(-/-) mice was ~20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTgSod1(-/-) mice compared with control animals, whereas muscles of age-matched Sod1(-/-) mice displayed 30-40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1(-/-) mice were absent in SynTgSod1(-/-) mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1(-/-) mice but not in SynTgSod1(-/-) mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1(-/-) mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.

Differential cysteine labeling and global label-free proteomics reveals an altered metabolic state in skeletal muscle aging.

The molecular mechanisms underlying skeletal muscle aging and associated sarcopenia have been linked to an altered oxidative status of redox-sensitive proteins. Reactive oxygen and reactive nitrogen species (ROS/RNS) generated by contracting skeletal muscle are necessary for optimal protein function, signaling, and adaptation. To investigate the redox proteome of aging gastrocnemius muscles from adult and old male mice, we developed a label-free quantitative proteomic approach that includes a differential cysteine labeling step. The approach allows simultaneous identification of up- and downregulated proteins between samples in addition to the identification and relative quantification of the reversible oxidation state of susceptible redox cysteine residues. Results from muscles of adult and old mice indicate significant changes in the content of chaperone, glucose metabolism, and cytoskeletal regulatory proteins, including Protein DJ-1, cAMP-dependent protein kinase type II, 78 kDa glucose regulated protein, and a reduction in the number of redox-responsive proteins identified in muscle of old mice. Results demonstrate skeletal muscle aging causes a reduction in redox-sensitive proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response. Data is available via ProteomeXchange with identifier PXD001054.

Application of redox proteomics to skeletal muscle aging and exercise.

Skeletal muscle represents a physiologically relevant model for the application of redox proteomic techniques to dissect its response to exercise and aging. Contracting skeletal muscles generate ROS (reactive oxygen species) and RNS (reactive nitrogen species) necessary for the regulation of many proteins involved in excitation-contraction coupling. The magnitude and species of ROS/RNS generated by contracting muscles will have downstream effects on specific protein targets and cellular redox signalling. Redox modifications on specific proteins are essential for the adaptive response to exercise and skeletal muscle can develop a dysregulated redox response during aging. In the present article, we discuss how redox proteomics can be applied to identify and quantify the reversible modifications on susceptible cysteine residues within those redox-sensitive proteins, and the integration of oxidative and non-oxidative protein modifications in relation to the functional proteome.

Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle.

Increased oxidative damage and disrupted redox signalling are consistently associated with age-related loss of skeletal muscle mass and function. Redox signalling can directly regulate biogenesis and degradation pathways and indirectly via activation of key transcription factors. Contracting skeletal muscle fibres endogenously generate free radicals (e.g. superoxide) and non-radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling can promote beneficial adaptive responses that are disrupted by age-related redox changes. Identifying and quantifying the redox signalling pathways responsible for successful adaptation to exercise makes skeletal muscle an attractive physiological model for redox proteomic approaches. Site specific identification of the redox modification and quantification of site occupancy in the context of protein abundance remains a crucial concept for redox proteomics approaches. Notwithstanding, the technical limitations associated with skeletal muscle for proteomic analysis, we discuss current approaches for the identification and quantification of transient and stable redox modifications that have been employed to date in ageing research. We also discuss recent developments in proteomic approaches in skeletal muscle and potential implications and opportunities for investigating disrupted redox signalling in skeletal muscle ageing.

Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle.

AIMS: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1-/-) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1-/- mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1-/- mice, we characterized neuromuscular changes in the Sod1-/- model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle. RESULTS: In contrast to mSod1KO mice, myofiber atrophy in Sod1-/- mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic analyses confirmed increased proteasomal activity and adaptive stress responses in muscle of Sod1-/- mice that were absent in mSod1KO mice. Peripheral nerve from neither Sod1-/- nor mSod1KO mice showed increased oxidative damage or molecular responses to increased oxidation compared with wild type mice. Differential cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1-/- mice. Innovation and Conclusion: These findings demonstrate that neuromuscular integrity, redox mechanisms, and pathways are differentially altered in nerve and muscle of Sod1-/- and mSod1KO mice. Results support the concept that impaired redox signaling, rather than oxidative damage, in peripheral nerve plays a key role in muscle loss in Sod1-/- mice and potentially sarcopenia during aging. Antioxid. Redox Signal. 28, 275-295.

Redox homeostasis and age-related deficits in neuromuscular integrity and function.

Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age-related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this 'epidemic' problem, the primary biochemical and molecular mechanisms underlying age-related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age-associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age-related muscle atrophy and weakness.

Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England.

OBJECTIVE: Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites. DESIGN: Cohort study. SETTING: UK university hospital, recruiting from April 2014 to April 2015. PARTICIPANTS: Ninety-two patients with CFS/ME and 94 age-matched healthy controls (HCs). MAIN OUTCOME MEASURES: The presence of a significant association between CFS/ME, fatigue and vitamin D measures. RESULTS: No evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2 and 25(OH)D3 metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels. CONCLUSIONS: Low serum concentrations of total 25(OH)D do not appear to be a contributing factor to the level of fatigue of CFS/ME.

Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy.

Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging.

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice.

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damage.

Redox proteomic analysis of the gastrocnemius muscle from adult and old mice.

The data provides information in support of the research article, "Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging", Journal of Proteome Research, 2014, 13 (11), 2008-21 [1]. Raw data is available from ProteomeXchange [2] with identifier PDX001054. The proteome of gastrocnemius muscle from adult and old mice was analyzed by global label-free proteomics and the relative quantification of specific reduced and reversibly oxidized Cysteine (Cys) residues was performed using Skyline [3]. Briefly, reduced Cysteine (Cys) containing peptides was alkylated using N-ethylmalemide (d0-NEM). Samples were desalted and reversibly oxidized Cys residues were reduced using tris(2-carboxyethyl)phosphine (TCEP) and the newly formed reduced Cys residues were labeled with heavy NEM( d5-NEM). Label-free analysis of the global proteome of adult (n=5) and old (n=4) gastrocnemius muscles was performed using Peaks7™ mass spectrometry data analysis software [4]. Relative quantification of Cys containing peptides that were identified as reduced (d(0) NEM labeled) and reversibly oxidized d(5)-NEM labeled was performed using the intensity of their precursor ions in Skyline. Results indicate that muscles from old mice show reduced redox flexibility particularly in proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response.

SS-31 attenuates TNF-α induced cytokine release from C2C12 myotubes.

TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the mitochondrial generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the effect of TNF-α on the production of myokines by skeletal muscle. Significant increases were seen in the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of cytokines by muscle cells. An increase was also seen in superoxide in response to treatment with TNF-α, which was localised to the mitochondria and this was also associated with activation of NF-κB. The changes in superoxide, activation of NF-kB and release of myokines were attenuated following pre-treatment with SS-31 peptide indicating that the ability of TNF-α to induce myokine release may be mediated through mitochondrial superoxide, which is, at least in part, associated with activation of the redox sensitive transcription factor NF-kB.

Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype.

Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study, we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness. The nSod1KO mice show a significant loss of CuZnSOD activity and protein level in brain and spinal cord but not in muscle tissue. The masses of the gastrocnemius, tibialis anterior and extensor digitorum longus (EDL) muscles were not reduced in nSod1KO compared to wild type mice, even at 20 months of age, although the quadriceps and soleus muscles showed small but statistically significant reductions in mass in the nSod1KO mice. Maximum isometric specific force was reduced by 8-10% in the gastrocnemius and EDL muscle of nSod1KO mice, while soleus was not affected. Muscle mitochondrial ROS generation and oxidative stress measured by levels of reactive oxygen/nitrogen species (RONS) regulatory enzymes, protein nitration and F2-isoprostane levels were not increased in muscle from the nSod1KO mice. Although we did not find evidence of denervation in the nSod1KO mice, neuromuscular junction morphology was altered and the expression of genes associated with denervation acetylcholine receptor subunit alpha (AChRα), the transcription factor, Runx1 and GADD45α) was increased, supporting a role for neuronal loss of CuZnSOD initiating alterations at the neuromuscular junction. These results and our previous studies support the concept that CuZnSOD deficits in either the motor neuron or muscle alone are not sufficient to initiate a full sarcopenic phenotype and that deficits in both tissues are required to recapitulate the loss of muscle observed in Sod1KO mice.

Role of superoxide-nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase.

Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1(-/-) mice were loaded with NO-sensitive (4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1(-/-) mice compared with those from WT mice. Fibers from Sod1(-/-) mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1(-/-) mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1(-/-) mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1(-/-) mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle.

Ergogenic and antioxidant effects of spirulina supplementation in humans.

PURPOSE: Spirulina is a popular nutritional supplement that is accompanied by claiMSS for antioxidant and performance-enhancing effects. Therefore, the aim of the present study was to examine the effect of spirulina supplementation on (i) exercise performance, (ii) substrate metabolism, and (iii) blood redox status both at rest and after exercise. METHODS: Nine moderately trained males took part in a double-blind, placebo-controlled, counterbalanced crossover study. Each subject received either spirulina (6 g x d(-1)) or placebo for 4 wk. Each subject ran on a treadmill at an intensity corresponding to 70%-75% of their VO2max for 2 h and then at 95% VO2max to exhaustion. Exercise performance and respiratory quotient during exercise were measured after both placebo and spirulina supplementation. Blood samples were drawn before, immediately after, and at 1, 24, and 48 h after exercise. Reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, thiobarbituric acid-reactive substances (TBARS), protein carbonyls, catalase activity, and total antioxidant capacity (TAC) were determined. RESULTS: Time to fatigue after the 2-h run was significantly longer after spirulina supplementation (2.05 +/- 0.68 vs 2.70 +/- 0.79 min). Ingestion of spirulina significantly decreased carbohydrate oxidation rate by 10.3% and increased fat oxidation rate by 10.9% during the 2-h run compared with the placebo trial. GSH levels were higher after the spirulina supplementation compared with placebo at rest and 24 h after exercise. TBARS levels increased after exercise after placebo but not after spirulina supplementation. Protein carbonyls, catalase, and TAC levels increased similarly immediately after and 1 h after exercise in both groups. CONCLUSIONS: Spirulina supplementation induced a significant increase in exercise performance, fat oxidation, and GSH concentration and attenuated the exercise-induced increase in lipid peroxidation.

Favorable and prolonged changes in blood lipid profile after muscle-damaging exercise.

PURPOSE: To examine the effect of repeated muscle-damaging exercise on the time-course changes in blood lipid and lipoprotein profile and compare them with changes in indices of muscle function and damage. METHODS: Twelve women underwent an isokinetic exercise session consisting of 75 eccentric knee flexions, which was repeated after 3 wk. Triacylglycerols (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDLC) in plasma were measured before, immediately, 1, 2, 3, 4, and 7 d after muscle-damaging exercise. Low-density lipoprotein cholesterol (LDLC) and TC/HDLC were also calculated. RESULTS: The largest changes in TG and lipoproteins appeared 3 d after exercise, returning toward baseline thereafter. The magnitudes of these changes at 3 d compared with rest were -18% and -8% for TG, -14% and -10% for TC, 8% and 7% for HDLC, -25% and -18% for LDLC, and -20% and -15% for TC/HDLC after sessions 1 and 2, respectively. In addition, the incremental or decremental area under the curve for the TG and lipoproteins measured after the first session was higher than that after the second session--except for HDLC concentration. CONCLUSION: These findings reveal that lipid and lipoprotein profile was favorably affected by both sessions of muscle-damaging exercise but relatively less so after a repeated session of muscle-damaging exercise.