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Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P

Patients with Duchenne muscular dystrophy (DMD) have reduced muscle function due to chronic muscle damage, inflammation, oxidative stress, and reduced oxidative capacity. Resveratrol reduces inflammation and oxidative stress, and increases oxidative capacity in other disease models. The purpose of this study was to determine the effects of resveratrol on muscle function, muscle pathology, and oxidative capacity in young mdx mice. For this, 4- to 5-week-old male mdx mice were randomized into control or resveratrol-treated groups and given resveratrol (100 mg/kg body mass) or an equal volume of water by gavage every other day for 8 weeks. Muscle function was assessed pre- and post-treatment. Central nucleation, total immune cell infiltrate, oxidative stress, and oxidative capacity were measured post-treatment. Resveratrol mediated substantial improvements in rotarod performance and in-situ peak tension by 53% and 17%, respectively, and slight improvements in central nucleation and oxidative stress. Resveratrol did not affect total immune cell infiltrate at 12 weeks of age, and had no effect on oxidative capacity. Resveratrol improves muscle function in mdx mice despite small changes in muscle pathology. The likely mechanism is a resveratrol-mediated reduction in immune cell infiltrate at the early stages of this disease, as previously reported by our laboratory. Key words: Duchenne muscular dystrophy, resveratrol, inflammation, oxidative stress, oxidative capacity, muscle damage, utrophin. Les patients atteints de la dystrophie musculaire de Duchesne (DMD) presentent une fonction musculaire reduite a cause d'un dommage musculaire chronique, d'une inflammation, d'un stress oxydant et d'une capacite oxydante reduite. Le resveratrol reduit l'inflammation et le stress oxydant, et il accroit la capacite oxydante dans d'autres modeles de maladies. Le but de cette etude etait d'evaluer les effets d'un traitement au resveratrol sur la fonction musculaire, la pathologie du muscle et la capacite oxydante de jeunes souris mdx. Des souris males mdx de 4-5 semaines ont ete reparties aleatoirement en groupes controles ou traites au resveratrol, et elles ont re^u le resveratrol (100 mg/kg) ou de l'eau a tous les deux jours pendant 8 semaines. La fonction musculaire a ete evaluee avant et apres le traitement. La nucleation centrale, l'infiltrat immunitaire total, le stress oxydant et la capacite oxydante ont ete mesures apres le traitement. Le resveratrol permettait d'obtenir des ameliorations substantielles de la performance au Rotarod et du pic de la tension in situ de 53% et 17%, respectivement, et une legere amelioration sur le plan de la nucleation centrale et du stress oxydant. Le resveratrol n'affectait pas l'infiltrat immunitaire total a l'age de 12 semaines et n'avait pas d'effet sur la capacite oxydante. Le resveratrol ameliore la fonction musculaire des souris mdx malgre de faibles changements sur le plan de la pathologie du muscle. Le mecanisme probable consiste en une reduction de l'infiltrat immunitaire dependante du resveratrol a des etapes precoces de cette maladie, comme rapporte precedemment par notre laboratoire. [Traduit par la Redaction] Mots-cles: dystrophie musculaire de Duchesne, resveratrol, inflammation, stress oxydant, capacite oxydante, dommage musculaire, utrophine., Introduction Duchenne muscular dystrophy (DMD) is the most common lethal genetic disease, affecting 1 in 3500 live male births (Hoffman et al. 1987). This disease is caused by mutations in [...]

Background. The alpha-actinin-3 (ACTN3) R577X polymorphism has been associated with muscle power performance in cross-sectional studies. Methods. We examined baseline knee extensor concentric peak power (PP) and PP change with ~10 weeks of unilateral knee extensor strength training (ST) using air-powered resistance machines in 71 older men (65 [standard deviation = 8] years) and 86 older women (64 [standard deviation = 9] years). Results. At baseline in women, the XX genotype group had an absolute (same resistance) PP that was higher than the RR (p = .005) and RX genotype groups (p = .02). The women XX group also had a relative (70% of one-repetition maximum [1-RM]) PP that was higher than that in the RR (p = .002) and RX groups (p = .008). No differences in baseline absolute or relative PP were observed between ACTN3 genotype groups in men. In men, absolute PP change with ST in the RR (n = 16) group approached a significantly higher value than in the XX group (n = 9; p = .07). In women, relative PP change with ST in the RR group (n = 16) was higher than in the XX group (n = 17; p = .02). Conclusions. The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults.

Abstract Background Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1) determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2) to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. Methods ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL)-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. Results Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2) protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1) was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression induced. Exercise normalized these IL-6 induced effects. C2C12 myotubes administered IL-6 had increased FIS1 protein expression, increased oxidative stress, and reduced PGC-1α gene expression without altered mitochondrial protein expression. Conclusions Altered expression of proteins regulating mitochondrial biogenesis and fusion are early events in the initiation of cachexia regulated by IL-6, which precede the loss of muscle mitochondrial content. Furthermore, IL-6 induced mitochondrial remodeling and proteolysis can be rescued with moderate exercise training even in the presence of high circulating IL-6 levels.

Abstract Background IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx) of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse. Methods A monoclonal antibody against the IL-6 receptor (IL-6r mAb) that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined. Results IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice. Conclusions These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice.

Objective This pilot trial examined the effects of a combined intervention of mindfulness meditation followed by aerobic walking exercise compared with a control condition in chronic low back pain patients. We hypothesized that meditation before exercise would reduce disability, pain, and anxiety by increasing mindfulness prior to physical activity compared with an audiobook control group. Participants Thirty-eight adults completed either meditation and exercise treatment (MedExT) (n=18) or an audiobook control condition (n=20). Setting Duquesne University Exercise Physiology Laboratory. Design A pilot, assessor-blinded, randomized controlled trial. Methods Over a 4-week period, participants in the MedExT group performed 12–17 minutes of guided meditation followed by 30 minutes of moderate-intensity walking exercise 5 days per week. Measures of disability, pain, mindfulness, and anxiety were taken at baseline and postintervention. Pain perception measurements were taken daily. Results Compared with the control group, we observed larger improvements in disability in the MedExT intervention, although the changes were modest and not statistically significant (mean between-group difference, –1.24; 95% confidence interval [CI], –3.1 to 0.6). For secondary outcome measures, MedExT increased mindfulness (within-group) from pre-intervention to postintervention (P =0.0141). Additionally, mean ratings of low back pain intensity and unpleasantness significantly improved with time for the MedExT group compared with that of the control group, respectively (intensity P =0.0008; unpleasantness P =0.0022). Conclusion. Overall, 4 weeks of MedExT produced suggestive between-group trends for disability, significant between-group differences for measures of pain, and significant within-group increases in mindfulness. [ABSTRACT FROM AUTHOR]

To determine sex and race differences in muscle power per unit of muscle contraction, knee-extensor muscle power normalized for knee-extensor muscle volume was measured in 79 middle-aged and older adults (30 men and 49 women, age range 50–85 years). Results revealed that women displayed a 38% faster peak movement velocity than men and African Americans had a 14% lower peak movement velocity than Whites of a similar age when expressed per unit of involved muscle (p < .001). As expected, men exhibited greater knee-extensor strength and peak power per unit of muscle than women, but women had a faster knee-extension movement velocity per unit of muscle than men at the same relative strength level. Moreover, African Americans had greater knee-extensor muscle volume than Whites but exhibited lower knee-extensor strength and lower movement velocity per unit of muscle when tested at the same relative strength levels. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence purports exercise as a first-line therapeutic for the treatment of nearly all forms of chronic pain. However, knowledge of efficacious dosing respective to treatment modality and pain condition is virtually absent in the literature. The purpose of this analysis was to calculate the extent to which exercise treatment shows dose-dependent effects similar to what is seen with pharmacological treatments. Methods: A recently published comprehensive review of exercise and physical activity for chronic pain in adults was identified in May 2017. This report reviewed different physical activity and exercise interventions and their effectiveness in reducing pain severity and found overall modest effects of exercise in the treatment of pain. We analyzed this existing data set, focusing specifically on the dose of exercise intervention in these studies. We re-analyzed data from 75 studies looking at benefits of time of exercising per week, frequency of exercise per week, duration of intervention (in weeks), and estimated intensity of exercise. Results: Analysis revealed a significant positive correlation with exercise duration and analgesic effect on neck pain. Multiple linear regression modeling of these data predicted that increasing the frequency of exercise sessions per week is most likely to have a positive effect on chronic pain patients. Discussion: Modest effects were observed with one significant correlation between duration and pain effect for neck pain. Overall, these results provide insufficient evidence to conclude the presence of a strong dose effect of exercise in pain, but our modeling data provide tes predictions that can be used to design future studies to explicitly test the question of dose in specific patient populations. [ABSTRACT FROM AUTHOR]

Background: Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1) determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2) to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. Methods: ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL)-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. Results: Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2) protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1) was induced. IL-6receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α, and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression induced. Exercise normalized these IL-6 induced effects. C2C12 myotubes administered IL-6 had increased FIS1 protein expression, increased oxidative stress, and reduced PGC-1α gene expression without altered mitochondrial protein expression.Conclusions: Altered expression of proteins regulating mitochondrial biogenesis and fusion are early events in the initiation of cachexia regulated by IL-6, which precede the loss of muscle mitochondrial content. Furthermore, IL-6 induced mitochondrial remodeling and proteolysis can be rescued with moderate exercise training even in the presence of high circulating IL-6 levels. [ABSTRACT FROM AUTHOR]

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ mice that were either weight stable (WS) or had initial (≤5%), intermediate (6–19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process. [ABSTRACT FROM AUTHOR]

To examine the influence of insulin-like growth factor (IGF) pathway gene polymorphisms on muscle mass and strength responses to strength training (ST), we studied 128 White and Black men and women before and after a 10-wk single-leg knee extension ST program. One-repetition maximum strength, muscle volume (MV) via computed tomography, and muscle quality (MQ) were assessed at baseline and after 10 wk of ST. There was a significant combined IGFI cytosine adenine (CA) repeat gene effect, which included both the IGFI CA repeat main effect and IGFI CA repeat X PPP3RI insertion-deletion (l/D) gene X gene interaction effect, on the changes in strength (P < 0.01) and MQ (P < 0.05) with ST. There was a trend for a significant gene X gene interaction between IGFI CA repeat and PPP3RI l/D for changes in strength (P = 0.07) and MQ (P = 0.06) with ST. The influence of the PPP3RI A-202C gene polymorphism on change in MV with ST approached significance (P = 0.06). The IGFI CA repeat polymorphism had a significant influence on the change in strength and MV combined with ST (P < 0.05), whereas the influence of the PPP3RJ l/D polymorphism approached significance (P = 0.08). There were no associations between the IGFBP3 A-202C gene polymorphism and the muscle phenotypic responses to ST. These data suggest that two of the three IGF pathway gene polymorphisms identified in this study influence muscle phenotypic responses to ST in both Black and White older men and women. [ABSTRACT FROM AUTHOR]

The effects of a 10-wk unilateral knee extension strength training (ST) program on peak power (PP) and peak movement velocity (PV), at given absolute (force load) and relative (same % of 1 repetition maximum) resistances (loads), were examined in 30 older men [64 yr (7 SD)] and 32 older women [62 yr (6 SD)]. PP increased significantly in both men and women at the same absolute (P < 0.001) and relative loads (P < 0.01) with ST. Men had a significantly greater increase in relative PP than women with ST at 60% (P < 0.01) and 70% (P < 0.001) of 1 repetition maximum when covarying for baseline differences and age. However, when each subject was tested at the same absolute load and when PP was normalized for the muscle volume of the trained knee extensors (i.e., absolute muscle power quality), women increased by 9% (P < 0.05), whereas men did not change. Both men and women increased their absolute PV (P < 0.001) but decreased their relative PV significantly with ST (P < 0.05). However, when baseline values and age were covaried, women had significantly less of a decrease in relative PV quality with ST than men (P < 0.01), although the difference was small. These normalized data suggest that ST-induced increases in PP depend on muscular hypertrophy in men, but not in women, providing further support for the hypothesis developed from our previous report (Ivey FM, Tracy BL, Lemmer JT, NessAiver M, Metter EJ, Fozard JL and Hurley BF. J Gerontol A Biol Sci Med Sci 55: B 152-B 157, 2000) that improvements in muscle function with ST result from nonmuscle mass adaptations to a greater extent in women than men. [ABSTRACT FROM AUTHOR]

Strength training (ST) is considered an intervention of choice for the prevention and treatment of sarcopenia. Reports in the literature have suggested that the insulin-like growth factor I protein (IGF-I) plays a major role in ST-induced skeletal muscle hypertrophy and strength improvements. A microsatellite repeat in the promoter region of the IGF1 gene has been associated with IGF-I blood levels and phenotypes related to IGF-I in adult men and women. To examine the influence of this polymorphism on muscle hypertrophic and strength responses to ST, we studied 67 Caucasian men and women before and after a 10-wk single-leg knee-extension ST program. One repetition maximum strength, muscle volume via computed tomography, and muscle quality were assessed at baseline and after 10 wk of training. The IGF1 repeat promoter polymorphism and three single-nucleotide polymorphisms were genotyped. For the promoter polymorphism, subjects were grouped as homozygous for the 192 allele, heterozygous, or noncarriers of the 192 allele. After 10 wk of training, 1-repetition maximum, muscle volume, and muscle quality increased significantly for all groups combined (P < 0.001). However, carriers of the 192 allele gained significantly more strength with ST than noncarriers of the 192 allele (P = 0.02). There was also a nonsignificant trend for a greater increase in muscle volume in 192 carriers than noncarriers (P = 0.08). No significant associations were observed for the other polymorphisms studied. Thus these data suggest that the IGF1 promoter polymorphism may influence the strength response to ST. Larger sample sizes should be used in future studies to verify these results. [ABSTRACT FROM AUTHOR]

Knowledge of efficacious dosing respective to exercise type and pain condition is extremely limited in the literature. This study aimed to determine the impact of dose of moderate intensity treadmill walking on experimentally-induced pain in healthy human participants. Forty females were divided into 4 groups: control (no exercise), low dose exercise (3×/wk), moderate dose exercise (5×/wk) or high dose exercise (10×/wk). Over a 7-day period, subjects performed treadmill walking during assigned exercise days. Both qualitative and quantitative measures of pain were measured at baseline, during the trial, and 24 hrs post-final intervention session via sensitivity thresholds to painful thermal and painful pressure stimulation. Significant effects of treatment were found post-intervention for constant pressure pain intensity (p = 0.0016) and pain unpleasantness ratings (p = 0.0014). Post-hoc tests revealed significant differences between control and moderate and control and high dose groups for constant pressure pain intensity (p = 0.0015), (p = 0.0094), respectively and constant pressure pain unpleasantness (p = 0.0040), (p = 0.0040), respectively. Moderate and high dose groups had the greatest reductions in ratings of pain, suggesting that our lowest dose of exercise was not sufficient to reduce pain and that the moderate dose of exercise may be a sufficient starting dose for exercise-based adjuvant pain therapy. [ABSTRACT FROM AUTHOR]

The article reviews the article "Can Aerobic Training Improve Muscle Strength and Power in Older Men?," by D.I. Lovell, R. Cuneo, and G.C. Gass, which appeared in the periodical "Journal of Aging & Physical Activity" in 2010.

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually. Concussion as defined by the 2013 Concussion Consensus Statement "may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an 'impulsive' force transmitted to the head." Concussions leave the individual with both short- and long-term effects. The short-term effects of sport related concussions may include changes in playing ability, confusion, memory disturbance, the loss of consciousness, slowing of reaction time, loss of coordination, headaches, dizziness, vomiting, changes in sleep patterns and mood changes. These symptoms typically resolve in a matter of days. However, while some individuals recover from a single concussion rather quickly, many experience lingering effects that can last for weeks or months. The factors related to concussion susceptibility and the subsequent recovery times are not well known or understood at this time. Several factors have been suggested and they include the individual's concussion history, the severity of the initial injury, history of migraines, history of learning disabilities, history of psychiatric comorbidities, and possibly, genetic factors. Many studies have individually investigated certain factors both the short-term and long-term effects of concussions, recovery time course, susceptibility and recovery. What has not been clearly established is an effective multifaceted approach to concussion evaluation that would yield valuable information related to the etiology, functional changes, and recovery. The purpose of this manuscript is to show one such multifaceted approached which examines concussions using computerized neurocognitive testing, event related potentials, somatosensory perceptual responses, balance assessment, gait assessment and genetic testing.

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+) mouse is not known. Cachexia progression was studied in Apc(Min/+) mice that were either weight stable (WS) or had initial (≤5%), intermediate (6-19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

Resistance training using lengthening (eccentric) contractions induces greater increases in muscle size than shortening (concentric) contractions, but the underlying molecular mechanisms are not clear. Using temporal expression profiling, we compared changes in gene expression within 24 h of an acute bout of each type of contractions conducted simultaneously in the quadriceps of different legs. Five healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise and 3, 6, and 24 h afterwards, in the fed state. Expression profiling (n = 3) was performed using a custom-made Affymetrix MuscleChip containing probe sets of approximately 3,300 known genes and expressed sequence tags expressed in skeletal muscle. We identified 51 transcripts differentially regulated between the two exercise modes. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). Using quantitative RT-PCR (n = 5), we verified expression changes (lengthening/shortening) in SIX1 (3 h, -1.9-fold, P < 0.001), CSRP3 (6 h, 2.9-fold, P < 0.05), and MUSTN1 (24 h, 4.3-fold, P < 0.05). We examined whether FBXO32/atrogin-1/MAFbx, a known regulator of protein breakdown and of muscle atrophy was differentially expressed: the gene was downregulated after lengthening contractions (3 h, 2.7-fold, P < 0.05; 6 h, 3.3-fold, P < 0.05; 24 h, 2.3-fold, P < 0.05). The results suggested that lengthening and shortening contractions activated distinct molecular pathways as early as 3 h postexercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise.