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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.

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]