Differences in skeletal muscle between men and women with chronic heart failure

Men with chronic heart failure (CHF) have alterationsin their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar tothose observed in men and if these alterations are related to exerciseintolerance. Twenty-five men and thirteen women with CHFperformed a maximal exercise test for evaluation of peak oxygen consumption (O₂) and resting leftventricular ejection fraction, after which a biopsy of the vastuslateralis was performed. Twenty-one normal subjects (11 women, 10 men)were also studied. The relationship between muscle markers and peakO₂ was consistent for CHF men and women.When controlling for gender, analysis showed that oxidative enzymes andcapillary density are the best predictors of peak O_2. These results indicatethat aerobically matched CHF men and women have no differences inskeletal muscle biochemistry and histology. However, when CHF groupswere separated by peak exercise capacity of 4.5 metabolic equivalents(METs), CHF men with peak O₂ >4.5METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenasecompared with CHF men with peak O₂ <4.5METs. CHF men with a lower peak O₂ hadincreased capillary density compared with men with higher peakO₂. These observations were notreproduced in CHF women. This suggests that differences may existin how skeletal muscle adapts to decreasing peakO₂ in patients with CHF.

     

Skewed macrophage polarization in aging skeletal muscle

Skeletal muscle aging is a major cause of disability and frailty in the elderly. The progressive impairment of skeletal muscle function with aging was recently linked to a disequilibrium between damage and repair. Macrophages participate in muscle tissue repair, first as pro‐inflammatory M1 subtype and then as anti‐inflammatory M2 subtype. However, information on the presence of macrophages in skeletal muscle is still sporadic and the effect of aging on macrophage phenotype remains unknown. In this study, we sought to characterize the polarization status of macrophages in skeletal muscle of persons across a wide range of ages. We found that most macrophages in human skeletal muscle are M2, and that this number increased with advancing age. On the contrary, M1 macrophages declined with aging, making the total number of macrophages invariant with older age. Notably, M2 macrophages colocalized with increasing intermuscular adipose tissue (IMAT) in aging skeletal muscle. Similarly, aged BALB/c mice showed increased IMAT and M2 macrophages in skeletal muscle, accompanied by slightly increased collagen protein production. Collectively, we report that polarization of macrophages to the major M2 subtype is associated with IMAT and propose that increased M2 in aged skeletal muscle may impact upon muscle metabolism associated with aging.     

The ketogenic diet preserves skeletal muscle with aging in mice

The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age and the potential molecular mechanisms of this action. Twelve‐month‐old mice were assigned to an isocaloric control or KD until 16 or 26 months of age, at which time skeletal muscle was collected for evaluating mass, morphology, and biochemical properties. Skeletal muscle mass was significantly greater at 26 months in the gastrocnemius of mice on the KD. This result in KD mice was associated with a shift in fiber type from type IIb to IIa fibers and a range of molecular parameters including increased markers of NMJ remodeling, mitochondrial biogenesis, oxidative metabolism, and antioxidant capacity, while decreasing endoplasmic reticulum (ER) stress, protein synthesis, and proteasome activity. Overall, this study shows the effectiveness of a long‐term KD in mitigating sarcopenia. The diet preferentially preserved oxidative muscle fibers and improved mitochondrial and antioxidant capacity. These adaptations may result in a healthier cellular environment, decreasing oxidative and ER stress resulting in less protein turnover. These shifts allow mice to better maintain muscle mass and function with age.     

Differences in nutritional outcomes between Brazilian white and black children

This paper analyzes whether differences in nutritional outcomes between white and black children are related to disparities in socioeconomic status and how improvements in nutritional indicators for each racial group over time are associated with changes in household income, parent's education and other socioeconomic attributes. According to the results, the gap in anthropometric measures would be substantially reduced if black and white children had similar characteristics. Evidence also shows that better economic and social attributes explain only a small part of the large improvement in nutritional measures verified between 2002-2003 and 2008-2009 for both racial groups.     

Neural control of aging skeletal muscle

Functional and structural decline in the neuromuscular system with aging has been recognized as a cause of impairment in physical performance and loss of independence in the elderly. Alterations in spinal cord motor neurones and at the neuromuscular junction have been identified as evidence of denervation in skeletal muscles from aging mammals, including humans. However, the reciprocal influences of neurones on gene expression in muscle and of muscle on age-related neurodegeneration are poorly understood, and, as a result, interventions aimed at delaying or preventing degeneration of the neural component in aging muscle have been largely unsuccessful. The present article discusses the evidence for neural influence on age-related impairments of skeletal muscle, including a role in excitation-contraction uncoupling. The role of nerves in regulating the trophic actions of insulin-like growth factor-1 (IGF-1) and other neurotrophic factors is considered as a novel influence on the effects of aging on the neuromuscular junction. A better understanding of nerve-muscle interactions will allow for more rational interventions in the aging neuromuscular system.     

Differences between smooth and skeletal muscle myosins in their interactions with F-actin

Myosin and F-actin were prepared from bovine carotid arterial smooth muscle and the properties of the binding of myosin to F-actin were compared with those of the binding of skeletal muscle myosin to F-actin. The following differences were observed between skeletal and smooth muscle myosins. 1. The rate of ATP-induced dissociation of arterial actomyosin was equal to that of hybrid actomyosin reconstituted from arterial myosin and skeletal muscle F-actin, but was much lower than those of skeletal muscle actomyosin and of hybrid actomyosin reconstituted from skeletal muscle myosin and arterial F-actin. 2. The amount of ATP necessary for complete dissociation of arterial actomyosin was 2 mol/mol of myosin, although it is well known that skeletal muscle actomyosin is dissociated completely by the addition of 1 mol ATP per mol of myosin. 3. Arterial actomyosin and hybrid actomyosin reconstituted from arterial myosin and skeletal muscle F-actin did not dissociate upon addition of 0.1 mM PPi, while skeletal muscle actomyosin dissociated completely. 4. In the absence of Mg2+, neither dissociation by ATP nor ATPase [EC 3.6.1.3] activity was observed with arterial actomyosin and hybrid actomyosin reconstituted from arterial myosin and skeletal muscle F-actin. On the other hand, skeletal muscle actomyosin dissociated almost completely upon addition of ATP and showed a considerably high ATPase activity. These observations reveal marked differences between myosins from skeletal and smooth muscles in their binding properties to F-actin.     

Low intrinsic running capacity is associated with reduced skeletal muscle substrate oxidation and lower mitochondrial content in white skeletal muscle

Chronic metabolic diseases develop from the complex interaction of environmental and genetic factors, although the extent to which each contributes to these disorders is unknown. Here, we test the hypothesis that artificial selection for low intrinsic aerobic running capacity is associated with reduced skeletal muscle metabolism and impaired metabolic health. Rat models for low- (LCR) and high- (HCR) intrinsic running capacity were derived from genetically heterogeneous N:NIH stock for 20 generations. Artificial selection produced a 530% difference in running capacity between LCR/HCR, which was associated with significant functional differences in glucose and lipid handling by skeletal muscle, as assessed by hindlimb perfusion. LCR had reduced rates of skeletal muscle glucose uptake (～30%; P = 0.04), glucose oxidation (～50%; P = 0.04), and lipid oxidation (～40%; P = 0.02). Artificial selection for low aerobic capacity was also linked with reduced molecular signaling, decreased muscle glycogen, and triglyceride storage, and a lower mitochondrial content in skeletal muscle, with the most profound changes to these parameters evident in white rather than red muscle. We show that a low intrinsic aerobic running capacity confers reduced insulin sensitivity in skeletal muscle and is associated with impaired markers of metabolic health compared with high intrinsic running capacity. Furthermore, selection for high running capacity, in the absence of exercise training, endows increased skeletal muscle insulin sensitivity and oxidative capacity in specifically white muscle rather than red muscle. These data provide evidence that differences in white muscle may have a role in the divergent aerobic capacity observed in this generation of LCR/HCR.     

Correlation between skeletal calcium mass and muscle mass in man.

The measurements of total body potassium (TBK) and calcium (TBCa) were made on 317 subjects by the techniques of whole-body counting and total-body neutron activation analysis (TBNAA), respectively. The TBK/TBCa ratios are constant for normals over the age range studied. The males have more cellular mass (TBK) per unit skeletal mass (TBCa) than the females, as indicated by their respective TBK/TBCa ratios, 0.122 +/- 0.008 (1 SD), and 0.100 +/- 0.007 (1 SD). In general, patients with various metabolic disorders tend to follow the physiological trend found in the normals. In a number of metabolic disorders, the loss of TBK was usually approximately 60% of that of the TBCa when expressed in terms of the predicted normal values. This suggests that the mechanism causing the loss of calcium in physiological and altered metabolic states simultaneously involves both the skeleton and its associated musculature.     

Sarcolemmal carbonic anhydrase in red and white rabbit skeletal muscle

Sarcolemmal vesicles of white and red skeletal muscles of the rabbit were prepared by consecutive density gradient centrifugations in sucrose and dextran according to Seiler and Fleischer (1982, J. Biol. Chem. 257, 13,862-13,871). White and red muscle membrane fractions enriched in sarcolemma were characterized by high ouabain-sensitive Na+, K(+)-ATPase, by high Mg2(+)-ATPase activity, and by a high cholesterol content. Ca2(+)-ATPase activity, a marker enzyme for sarcoplasmic reticulum, was not detectable in the highly purified white and red muscle sarcolemmal fractions. White and red muscle sarcolemmal fractions exhibited no significant differences with regard to Na+, K(+)-ATPase, Mg2(+)-ATPase, and cholesterol. Specific activity of carbonic anhydrase in white muscle sarcolemmal fractions was 38 U.ml/mg and was 17.6 U.ml/mg in red muscle sarcolemma. Inhibition properties of sarcolemmal carbonic anhydrase were analyzed for acetazolamide, chlorzolamide, and cyanate. White muscle sarcolemmal carbonic anhydrase is characterized by inhibition constants, KI, toward acetazolamide of 4.6 X 10(-8) M, toward chlorzolamide of 0.75 X 10(-8) M, and toward cyanate of 1.3 X 10(-4) M. Red muscle sarcolemmal carbonic anhydrase is characterized by KI values toward acetazolamide of 8.1 X 10(-8) M, toward chlorzolamide of 6.3 X 10(-8) M, and toward cyanate of 0.81 X 10(-4) M. In contrast to the high specific carbonic anhydrase activities in sarcolemma, carbonic anhydrase activity in sarcoplasmic reticulum from white muscle varied between values of only 0.7 and 3.3 U.ml/mg. Carbonic anhydrase of red muscle sarcoplasmic reticulum ranged from 2.4 to 3.7 U.ml/mg.     

Signaling pathways controlling skeletal muscle mass

Abstract

The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy”, is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.     

Regenerative potential of human skeletal muscle during aging

In this study, we have investigated the consequences of aging on the regenerative capacity of human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate the in vivo turn-over and (ii) the proportion of satellite cells calculated as compared to the total number of nuclei in a muscle fibre. Two skeletal muscles which have different types of innervation were analysed: the biceps brachii, a limb muscle, and the masseter, a masticatory muscle. The biopsies were obtained from two groups: young adults (23 +/- 1.15 years old) and aged adults (74 +/- 4.25 years old). Our results showed that during adult life, minimum telomere lengths and mean telomere lengths remained stable in the two muscles. The mean number of myonuclei per fibre was lower in the biceps brachii than in the masseter but no significant change was observed in either muscle with increasing age. However, the number of satellite cells, expressed as a proportion of myonuclei, decreased with age in both muscles. Therefore, normal aging of skeletal muscle in vivo is reflected by the number of satellite cells available for regeneration, but not by the mean number of myonuclei per fibre or by telomere lengths. We conclude that a decrease in regenerative capacity with age may be partially explained by a reduced availability of satellite cells.     

Determinants of zinc intake in low-Income black and white pregnant women

A prospective study was conducted to evaluate and compare the determinants of dietary zinc intake in black and white low-income pregnant women. The study population consisted of 1298 low-income women (70% Black, 30% White) who received prenatal care at University Hospital at the University of Alabama in Birmingham from 1985 to 1989. Various maternal characteristics were evaluated at the first prenatal visit. Two 24 h recalls were obtained at 18 and 30 wk of gestation to calculate the intakes of dietary zinc and other nutrients. Student’st test, ξ², Pearson correlation coefficients, and multiple regression analyses were used to compare and evaluate the determinants of zinc and other nutrient intakes in Black and White subjects. The mean prepregnancy body mass index and the mean intake of zinc, energy, and all the other nutrients except calcium were significantly higher in Black than in White subjects. There was a significant correlation between zinc and energy intake (r- 0.69,p = 0.001). Age, marital status, parity, socioeconomic status, smoking, and alcohol intake were not significant predictors of zinc or other nutrient intakes. After adjusting for energy intake, race was the only significant predictor of dietary zinc intake. Race and energy intake explained 24% of the variation in zinc intake. Results of this study indicate that after adjusting for other covariates, race and energy intakes are the only predictors of zinc intake in low-income pregnant women.     

Differences in transport of fatty acids and expression of fatty acid transporting proteins in adipose tissue of obese black and white women

We have reported that the rate of de novo triglyceride (TG) synthesis by omental, but not subcutaneous, adipose tissue was higher in African-American women (AAW) than in Caucasian women (CAW). The purpose of this study was to explore the potential mechanisms underlying this increase. Toward that end, we determined the activities of key enzymes in the pathway of TG synthesis, the rates of uptake of fatty acids by adipocytes, mRNA and protein levels of the fatty acid-transporting proteins FAT/CD36 and FATP, and mRNA and protein levels of PPARgamma in omental fat of AAW and CAW. The results showed 1) no difference in the activity of phosphofructokinase, glycerol-3-phosphate dehydrogenase, or diacylglycerol acyltransferase; 2) a higher rate of fatty acid uptake by adipocytes of the AAW; 3) an increase in the mRNA and protein levels of CD36 and FATP4 in the fat of the AAW; and 4) an increase in the mRNA and protein levels of PPARgamma, which can stimulate the expression of CD36 and FATP. These results suggest that the increase in the transport of fatty acid, which is mediated by the overexpression of the transport proteins in the omental adipose tissue of the AAW, might contribute to the higher prevalence of obesity in AAW.     

The influence of skeletal muscle on systemic aging and lifespan

Epidemiological studies in humans suggest that skeletal muscle aging is a risk factor for the development of several age‐related diseases such as metabolic syndrome, cancer, Alzheimer's and Parkinson's disease. Here, we review recent studies in mammals and Drosophila highlighting how nutrient‐ and stress‐sensing in skeletal muscle can influence lifespan and overall aging of the organism. In addition to exercise and indirect effects of muscle metabolism, growing evidence suggests that muscle‐derived growth factors and cytokines, known as myokines, modulate systemic physiology. Myokines may influence the progression of age‐related diseases and contribute to the intertissue communication that underlies systemic aging.