Cross-sectional Area Of Type Research Articles

Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats

Autophagy is a subcellular degradation mechanism important for muscle maintenance. Hypertension induces well-characterized pathological changes to the heart and is associated with impaired function and increased apoptotic signalling in skeletal muscle. We examined whether essential hypertension affects several autophagy markers in skeletal and cardiac muscle. Immunoblotting and qRT-PCR were used to measure autophagy-related proteins/mRNA in multiple skeletal muscles as well as left ventricle (LV) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Skeletal muscles of hypertensive rats had decreased (P<0.01) cross-sectional area of type I fibres (e.g. soleus WKY: 2952.9±64.4μm(2) vs. SHR: 2579.9±85.8μm(2)) and a fibre redistribution towards a 'fast' phenotype. Immunoblot analysis revealed that some SHR skeletal muscles displayed a decreased LC3II/I ratio (P<0.05), but none showed differences in p62 protein. LC3 and LAMP2 mRNA levels were increased approx. 2-3-fold in all skeletal muscles (P<0.05), while cathepsin activity, cathepsin L mRNA and Atg7 protein were increased 16-17% (P<0.01), 2-3-fold (P<0.05) and 29-49% (P<0.01), respectively, in fast muscles of hypertensive animals. Finally, protein levels of BAG3, a marker of chaperone-assisted selective autophagy, were 18-25% lower (P<0.05) in SHR skeletal muscles. In the LV of SHR, LC3I and p62 protein were elevated 34% (P<0.05) and 47% (P<0.01), respectively. Furthermore, p62 mRNA was 68% higher (P<0.05), while LAMP2 mRNA was 45% lower (P<0.05), in SHR cardiac muscle. There was no difference in Beclin1, Atg7, Bnip3 or BAG3 protein in the LV between strains. These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension.

Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties

This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females). Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties. At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P > 0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P < 0.01) and strength (-5.9 %, P < 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (>30 %), peak power (>200 %) and unloaded shortening velocity (>50 %) were elicited at follow-up. Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

Costamere remodeling with muscle loading and unloading in healthy young men

Costameres are mechano-sensory sites of focal adhesion in the sarcolemma that provide a structural anchor for myofibrils. Their turnover is regulated by integrin-associated focal adhesion kinase (FAK). We hypothesized that changes in content of costamere components (beta 1 integrin, FAK, meta-vinculin, gamma-vinculin) with increased and reduced loading of human anti-gravity muscle would: (i) relate to changes in muscle size and molecular parameters of muscle size regulation [p70S6K, myosin heavy chain (MHC)1 and MHCIIA]; (ii) correspond to adjustments in activity and expression of FAK, and its negative regulator, FRNK; and (iii) reflect the temporal response to reduced and increased loading. Unloading induced a progressive decline in thickness of human vastus lateralis muscle after 8 and 34 days of bedrest (−4% and −14%, respectively; n = 9), contrasting the increase in muscle thickness after 10 and 27 days of resistance training (+5% and +13%; n = 6). Changes in muscle thickness were correlated with changes in cross-sectional area of type I muscle fibers (r = 0.66) and beta 1 integrin content (r = 0.76) at the mid-point of altered loading. Changes in meta-vinculin and FAK-pY397 content were correlated (r = 0.85) and differed, together with the changes of beta 1 integrin, MHCI, MHCII and p70S6K, between the mid- and end-point of resistance training. By contrast, costamere protein level changes did not differ between time points of bedrest. The findings emphasize the role of FAK-regulated costamere turnover in the load-dependent addition and removal of myofibrils, and argue for two phases of muscle remodeling with resistance training, which do not manifest at the macroscopic level.

Immobility and diminished skeletal muscle recovery with age: the sedentary myoblast.

Immobility and diminished skeletal muscle recovery with age: the sedentary myoblast.

Reference values for vastus lateralis fiber size and type in healthy subjects over 40 years old: a systematic review and metaanalysis

Skeletal muscle atrophy is a major systemic impairment in chronic diseases. Yet its determinants have been hard to identify because a clear research definition has not been agreed upon. The reduction in muscle fiber cross-sectional area (CSA) is a widely acknowledged marker of muscle atrophy, but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published. Thus, we aimed to systematically review the studies providing data on fiber CSA and fiber type proportion in the vastus lateralis of the quadriceps of healthy subjects (age >40 yr) and then to pool and analyze the data from the selected studies to determine reference values for fiber CSA. We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and identified 19 studies, including 423 subjects that matched the inclusion criteria. On the basis of fiber type and gender, the mean fiber CSA and the lower limits of normal (LLNs) were (%type I*60) + 1,743 μm(2) and (%type I*60) - 718 μm(2), respectively, for men; and (%type I*70) + 139 μm(2) and (%type I*70) - 1,485 μm(2), respectively, for women. There was no significant heterogeneity among subgroups of fiber type and gender. The pooled type I fiber proportion was 50.3% (LLN = 32.9%). In multivariate analysis, fiber CSA was significantly correlated with Vo2 peak (r = 190.92; P = 0.03), and type I fiber proportion was correlated with age (r = -0.024; P = 0.005), body mass index (r = 0.096; P = 0.005), and Vo2 peak (r = -0.053; P = 0.005). Our metaanalysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender. This analysis will be improved by prospective assessment in well-characterized healthy subjects.

Hindlimb Muscle Atrophy Occurs From Short-Term Undernutrition in Rats

The purpose of this study was to examine the effect of short-term (7 days) undernutrition on Type I (soleus) and Type II (plantaris, gastrocnemius) muscles in rats. Male Sprague-Dawley rats (N = 20) were randomly assigned to one of two groups: a control group (n = 10) in which animals were allowed to have water and pellets ad libitum and an undernourished group (n = 10) in which animals were allowed to have 37% of the total food intake of the control group and water ad libitum. Body weight and food intake were measured daily. After 7 days, rats were anesthetized and the soleus, plantaris, and gastrocnemius muscles and liver were dissected. Body weight, liver weight, muscle weight, Types I and II fiber cross-sectional area, and myofibrillar protein content were determined. After 7 days of undernutrition, the undernourished group showed significant decreases (p < .05) compared to the control group in body weight, liver weight, muscle weight of soleus, plantaris, and gastrocnemius muscles, and cross-sectional areas of Types I and II fiber of the plantaris and gastrocnemius muscles.

Characteristics of Muscle Fibers in Rats with Limb Movements during Sleep after Spinal Cord Injury

Background/Aims: Previous studies have demonstrated that spinal cord injury (SCI) results in changes in sleep patterns through increased arousals and limb movements during sleep. Dramatic changes in muscle myosin heavy-chain isoforms have also been reported. The aim of this study was to investigate the characteristics of muscle fibers after SCI in rats with limb movements during sleep. Methods: Forty male Wistar rats were divided into four groups: SHAM, SCI 3, 7 and 15 days. Animals were subjected to electrode insertion surgery, 24-hour baseline sleep recording, SCI, and subsequent sleep recording for 3, 7, or 15 consecutive days. In addition, the gastrocnemius muscle and spinal cord were collected for histopathological/histochemical analyses. Results: Our results indicate a rapid and progressive decrease in the cross-sectional area of type I fibers in the gastrocnemius muscle (35.76–24.74 µm²) after SCI. Additionally, we found SCI-induced changes in sleep patterns. Following SCI, we also observed limb movements in sleeping rats, as well as significant negative moderate correlations between type I fibers and limb movement. Conclusion: Our study strengthened the hypothesis by correlation between changes in types of muscle fiber (decline in type I fibers) and an increase in limb movements during sleep after SCI.

Myostatin allelic status interacts with level of nutrition to affect growth, composition, and myofiber characteristics of lambs1

The objective of this experiment was to determine if growth, carcass composition, and myofiber characteristics of lambs were affected by heterozygosity for a myostatin mutation (g+6723G>A) when offered differing allowances of feed administered with or without ractopamine. Heterozygote [MSTN A/G (n = 40)] and homozygote wildtype [MSTN G/G (n = 39)] castrate male lambs were individually fed ad libitum (HI; 1.8 × estimated ME(m)) or a restricted allowance (LO; 1.1 × estimated ME(m)) of a diet (191 g of CP/kg of DM and 12 MJ of ME/kg of DM), supplemented with (0.4 mg/kg of BW) or without the β-adrenergic agonist ractopamine (RAC or NO RAC) for 47 d. The lambs were scanned by computed tomography at the beginning and completion of the feeding experiment to calculate composition of lean, fat, and bone in the carcass component of the body. The MSTN A/G HI intake lambs had significantly greater total daily carcass growth (P = 0.045) and loin eye depth (P = 0.022) and tended to have a greater daily growth of lean (P = 0.09) in the carcass, compared with MSTN G/G HI intake lambs. Conversely, MSTN A/G LO intake lambs tended to have less daily lean deposition (P = 0.09), significantly less total daily carcass growth (P = 0.045), and had a greater percentage of type IIX myofibers (P < 0.01) and total myofiber area (relative area) of type IIX myofibers (P = 0.013). The inclusion of RAC increased final BW (P = 0.03) and ADG (P = 0.02), percentage of type IIC (P < 0.001) and IIA (P = 0.012) myofibers, cross-sectional area of types I (P = 0.04) and IIAX (P = 0.04) fibers, and the relative area of type IIC (P = 0.003) and IIA (P = 0.01) myofibers in the LM. The experiment demonstrated that including RAC in the diet of lambs increased final BW and ADG, but not HCW, and increased proportion of type IIC and IIA myofibers and cross-sectional area of type I and IIAX myofibers. Our data suggest that RAC and the heterozygous myostatin mutation act together to increase growth of muscle on a high plane of nutrition. The experiment also demonstrated that poor nutritional background of lambs heterozygous for the myostatin mutation may negatively influence their growth rates and myofiber characteristics.

Randomized, Double-Blind, and Placebo-Controlled Trial of Clenbuterol in Denervated Muscle Atrophy

Objectives. β 2-adrenergic agonists, such as clenbuterol, have been shown to promote the hypertrophy of healthy skeletal muscles and to ameliorate muscle wasting in a few pathological conditions in both animals and humans. We intended to investigate the clinical efficacy of clenbuterol on attenuating denervation-induced muscle atrophy. Methods. A double-blind, placebo-controlled, parallel, and randomized trial was employed. 71 patients, suffering from brachial plexus injuries, were given either clenbuterol (60 μg, bid) or placebo for 3 months. Before and at the end of the study, patients were given physical examinations, biopsies of biceps brachii, electromyograms (EMGs), and other laboratory tests. Results. Compared with placebo treatment, clenbuterol significantly mitigated the decreases in cross-sectional areas of type I and II muscle fibers and alleviated the reduction in fibrillation potential amplitudes, without any adverse effects. Conclusions. Clenbuterol safely ameliorated denervated muscle atrophy in this cohort; thus larger clinical studies are encouraged for this or other β 2 agonists on denervation-induced muscle atrophy.

Anabolic effect of plant brassinosteroid

Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC(50) 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross-sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.

Qualitative and quantitative changes in skeletal muscle from heart failure patients

The objective of this study was to determine if functional deficits in skeletal muscle of heart failure (HF) patients are related to changes at the single fiber level. We examined protein content, ultrastructure and mechanical properties of single fibers from HF patients and sedentary controls. Overall, myosin heavy chain (MHC) protein content was reduced 19% (p&lt;0.01) with HF. In single fibers, MHC content was reduced 15% in Type I (p=0.06) and 19% in Type IIA (p&lt;0.04) with HF. These qualitative decreases in MHC content were associated with a 12% reduction in force production per cross‐sectional area in Type I fibers (p&lt;0.05). No differences in thick to thin filament ratio or A‐band length were found suggesting that MHC loss occurs along the thick filament length. At low [Ca2+] (pCa 8), Type I fibers from HF examined with sinusoidal analysis produced less oscillatory work and had a higher frequency of maximum work (p&lt;0.05), indicating an increase in myosin kinetics. At high [Ca2+] (pCa 4.5), Type I and IIA HF fibers showed similar myosin kinetics, larger elastic moduli at low oscillation frequencies and greater oscillatory work than controls (p&lt;0.05). These results indicate that HF qualitatively modifies skeletal muscle performance at the single fiber level. Together, these qualitative and quantitative changes may conspire to impair whole muscle function in heart failure patients. Support: NIH HL‐077418 and AG‐031303.

Muscle fiber type characteristics in females with chronic obstructive pulmonary disease. A preliminary study

Chronic obstructive pulmonary disease (COPD) is known to elicit intrinsic abnormalities in male skeletal muscle. However, it is unclear to what extent these changes occur in women and whether they are fiber-type specific. We investigated fiber-type specific differences in selected histochemical properties in muscle obtained from women with moderate to severe COPD compared to healthy control (CON) women. Tissue was obtained from the vastus lateralis in five COPD patients (age 66.9 +/- 2.6 years; FEV1 = 43 +/- 7%) and eight CON (age 68 +/- 4.9 years; FEV1 = 113 +/- 4.2%). Compared to CON, the distribution (30.6 +/- 5.2 vs. 57.9 +/- 4.6%) and cross sectional area of type I (CSA, 5660 +/- 329 vs. 3586 +/- 257 microm2) and type IIA (2770 +/- 302 vs. 2099 +/- 206 microm2) were lower (P < 0.05) and higher (P < 0.05), respectively, in COPD. Disease state did not alter either the distribution or CSA of the IIA, IIAX or type X subtypes. Although differences were found between fiber types in the number of capillary contacts (n) (I > IIAX, IIX; IIA > IIX) and the capillaries per CSA (microm210(-3)) (I < IIA, IIAX, IIX), no differences were found between CON and COPD. Succinic dehydrogenase activity and sarcoplasmic reticulum (SR) Ca2+-ATPase activity, measured photometrically (OD units), were higher (P < 0.05), and lower (P < 0.05), respectively, in type I compared to the type II fiber subtypes. These properties were not altered with COPD. COPD in females is accompanied by a higher percent of type II fibers, a larger CSA of type I and type IIA fibers, both of which occur in the absence of differences in oxidative potential and the potential for SR Ca2+-sequestration.

Effects of taurine on alterations in structure and function of sternohyoid muscle in metabolic syndrome rats

To investigate the alterations in structure and function of sternohyoid muscle of metabolic syndrome (MS) rats effects and the effects of taurine thereupon contractile properties. Twenty-one healthy male SD rats were randomly assigned to three groups: control group (Group A, n=6) fed with normal food, MS group (Group B, n=8) fed with high-lipid forage for 9 weeks to induce MS and then fed with the same high-lipid forage for 12 weeks in addition, and taurine group (Group C, n=7), fed with high-lipid forage for 20 weeks and given gastric perfusion of taurine 50 mg x d(-1) x kg(-1) since the tenth week for 12 weeks. Venous blood samples were collected to undergo biochemical examination of plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose (Glu). Radioimmunoassay was used to detect the plasma insulin. The sternohyoid muscles were collected. Muscle tissue homogenate was made. The superoxide dismutase (SOD) and malondialdehy (MDA) levels were measured. Myosin-ATPase histochemistry was used to assay the size and capillary density of the isolated sternohyoid muscles. Isometric contractile properties were determined by electrostimulating the strips of isolated sternohyoid muscles at different frequencies (from 10 Hz to 100 Hz) to observe the changes of the sternohyoid contractile properties in different conditions. (1) The levels of TG, LDL, Glu, PGI, and MDA of Group B were significantly higher than those of Groups A and C, while the HDL level of Group B was significantly lower than that of Group A (P < 0.01). The OD level of Group B was significantly lower than those of Groups A and C. (2) The capillary density, capillary-to-fiber ratio (C/F), and cross-sectional area of type I fiber in sternohyoid muscles of Group B were (140 +/- 5)/ nm2, 0.90 +/- 0.11, and (6119 +/- 165) microm2 respectively, all significantly higher than those of Group A [(278 +/- 17)/mm2, 1.43 +/- 0.05, and (9371 +/- 68) microm2 respectively, all P < 0.01] and Group C [(269 +/- 10)/mm2, 1.40 +/- 0.07, and (9007 +/- 136) microm2 respectively, all P < 0.01]. (3) The tensions of sternohyoid muscle of Group B at the frequencies from 10 Hz to 60 Hz were (29 +/- 6) g/cm2, (34 +/- 7) g/ cm2, (41 +/- 6)g/cm2, (47 +/- 6)g/cm2, (53 +/- 7)g/cm2, and (59 +/- 20)g/cm2 respectively, all significantly lower than those of Group A group[(40 +/- 3)g/cm2, (52 +/- 13)g/cm2, (60 +/- 17) g/cm2, (74 +/- 32) g/cm2, (80 +/- 29)g/cm2, and (96 +/- 24)g/cm2 respectively, all P < 0.05] and Group C [(43 +/- 26)g/cm2, (48 +/- 6)g/cm2,(55 +/- 9)g/cm2, (67 +/- 14)g/cm2, (75 +/- 15)g/cm2, and (80 +/- 15)g/cm2 respectively, all P < 0.05]. (4) In fatigue test, the tension percentages of sternohyoid muscle at the time intervals of 1 min, 2 min, 3 min, 4 min, and 5 min of Group B were (80.5 +/- 8.0)%, (64.1 +/- 1.2)%, (59.1 +/- 1.1)%, (56.4 +/- 10.9)%, and (53.5 +/- 9.1)% respectively, all significantly lower than those of Group A [(87.7 +/- 3.5)%, (78.5 +/- 1.5)%, (76.0 +/- 1.2)%, (72.3 +/- 15.0)%, and (68.7 +/- 17.2)% respectively, all P < 0.05] and Group C group [(87.4 +/- 2.4)%, (77.9 +/- 5.5)%, (73.6 +/- 1.1)%, (71.3 +/- 8.7)%, and (68.0 +/- 6.7) respectively, all P < 0.05]. With the development of MS, the capillary density, C/F, cross-sectional area of type I fiber of upper airway muscles decrease, in part via oxidative stress, which leads to reduction of the contractile function of upper airway muscles, thus contributing to the onset of obstructive sleep apnea-hypopnea syndrome.

Anabolic effects of testosterone are preserved during inhibition of 5α-reductase

At replacement doses, testosterone produces only modest increases in muscle strength and bone mineral density in older hypogonadal men. Although higher doses of testosterone are more anabolic, there is concern over increased adverse effects, notably prostate enlargement. We tested a novel strategy for obtaining robust anabolic effects without prostate enlargement. Orchiectomized (ORX) male rats were treated for 56 days with 1.0 mg testosterone/day, with and without 0.75 mg/day of the 5alpha-reductase inhibitor MK-434. Testosterone administration elevated the prostate dihydrotestosterone concentration and caused prostate enlargement. Both effects were inhibited by MK-434. ORX produced a catabolic state manifested in reduced food intake, blunted weight gain, reduced hemoglobin concentration, decreased kidney mass, and increased bone resorption, and in the proximal tibia there was both decreased cancellous bone volume and a decreased number of trabeculae. In soleus and extensor digitorum longus muscles, ORX reduced both the percentage of type I muscle fibers and the cross-sectional area of type 1 and 2 fibers. Testosterone administration caused a number of anabolic effects, including increases in food intake, hemoglobin concentration, and grip strength, and reversed the catabolic effects of ORX on bone. Testosterone administration also partially reversed ORX-induced changes in muscle fibers. In contrast to the prostate effects of testosterone, the effects on muscle, bone, and hemoglobin concentration were not blocked by MK-434. Our study demonstrates that the effects of testosterone on muscle and bone can be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.

Morphological changes of skeletal muscle, tendon and periosteum in the senescence-accelerated mouse (SAMP6): A murine model for senile osteoporosis

SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. Previously we observed age-related changes of the bone in SAMP6. In the present study, we investigated the morphology of the skeletal muscle, tendon and periosteum in SAMP6 and age-matched normal mouse SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 and 2 months of age. As compared with SAMR1, the cross-sectional area of type I and type II muscle fibers of the soleus muscle were significantly low in SAMP6 at 8 months of age. The projections in the interface of the muscle–tendon junctions were significantly decreased in SAMP6 at 8 months of age. The number of fibroblasts and the diameter of the tendon collagen fibers in Achilles fiber were significantly reduced in SAMP6 at 8 months of age. The diameter of Sharpey's fiber reduced in SAMP6 at 5 and 8 months of age. Some chondrocytes in the insertions of Achilles tendon and some osteogenic cells in the periosteum showed degenerative changes in SAMP6 at 5 and 8 months of age. The pronounced degenerative changes were detected in the skeletal muscle, muscle–tendon junction, tendon, tendon–bone interface and periosteum in SAMP6 with age. These findings indicated the atrophy of skeletal muscle, degeneration of tendon and periosteum in SAMP6, which may be involved in the bone loss for senile osteoporosis.

Aging, muscle fiber type, and contractile function in sprint-trained athletes

Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V(o)) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V(o) of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V(o) of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V(o) of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

Age and sex affect human muscle fibre adaptations to heavy‐resistance strength training

This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20-30 years old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week(-1); the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P<0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres (P<0.05) along with a decrease in type IIx fibres (P=0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27-39%; all P<0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST.

Denervation effects on myonuclear domain size of rat diaphragm fibers

Denervation (DNV) of rat diaphragm muscle (DIAm) leads to selective atrophy of type IIx and IIb fibers, whereas the cross-sectional area of type I and IIa fibers remains unchanged or slightly hypertrophied. DIAm DNV also increases satellite cell mitotic activity and myonuclear apoptosis. Similar to other skeletal muscles, DIAm fibers are multinucleated, and each myonucleus regulates the gene products in a finite fiber volume, i.e., myonuclear domain (MND). MND size varies across DIAm fiber types in rank order, I < IIa < IIx < IIb [fiber type based on myosin heavy chain isoform expression]. We hypothesized that, after DNV, the total number of myonuclei per fiber does not change and, accordingly, that MND changes proportionately to the change in fiber size regardless of fiber type. Adult rats underwent unilateral (right side) DIAm DNV, and after 2 wk single fibers were dissected. Fiber cross-sectional area, myonuclear number, and MND were measured by confocal microscopy, and these values in DNV DIAm were compared with those obtained in controls. After DNV, type I fibers hypertrophied, type IIa fiber size was unchanged, and type IIx and IIb fibers atrophied compared with control. The total number of myonuclei per fiber was not affected by DNV. Accordingly, after DNV, type I fiber MND increased by 25%, whereas it decreased in type IIx and IIb fibers by 50 and 70%, respectively. These results suggest that MND is not maintained after DNV-induced DIAm fiber hypertrophy or atrophy. These results are interpreted with respect to consequent effects of DNV on myonuclear transcriptional activity and protein turnover.

Skeletal Muscle Adaptations to Interval Training in Patients With Advanced COPD

To investigate the response to interval exercise (IE) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle, and to compare these changes to those incurred after constant-load exercise (CLE) training. Randomized, controlled, parallel, two-group study (IE vs CLE training). Multidisciplinary, outpatient, hospital-based, pulmonary rehabilitation program. Nineteen patients with stable advanced COPD (mean +/- SEM FEV1, 40 +/- 4% predicted). Patients (n = 10) assigned to IE training exercised at a mean intensity of 124 +/- 15% of baseline peak exercise capacity (peak work rate [Wpeak]) with 30-s work periods interspersed with 30-s rest periods for 45 min/d. Patients (n = 9) allocated to CLE training exercised at a mean intensity of 75 +/- 5% Wpeak for 30 min/d. Patients exercised 3 d/wk for 10 weeks. Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation. After IE training, the cross-sectional areas of type I and IIa fibers were significantly increased (type I before, 3,972 +/- 455 microm2; after, 4,934 +/- 467 microm2 [p = 0.004]; type IIa before, 3,695 +/- 372 microm2; after, 4,486 +/- 346 microm2 [p = 0.008]), whereas the capillary-to-fiber ratio was significantly enlarged (from 1.13 +/- 0.08 to 1.24 +/- 0.07 [p = 0.013]). Citrate synthase activity increased (from 14.3 +/- 1.4 to 20.5 +/- 4.2 micromol/min/g), albeit not significantly (p = 0.097). There was also a significant improvement in Wpeak (by 19 +/- 5%; p = 0.04) and in lactate threshold (by 17 +/- 5%; p = 0.02). The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training. During training sessions, however, ratings of dyspnea and leg discomfort, expressed as fraction of values achieved at baseline Wpeak, were significantly lower (p < 0.05) for IE training (73 +/- 9% and 60 +/- 8%, respectively) compared to CLE training (83 +/- 10% and 87 +/- 13%, respectively). High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations; however, IE is associated with fewer training symptoms.

Effect of salbutamol on innervated and denervated rat soleus muscle

The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a beta2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10), treated with salbutamol (N = 30), denervated (N = 30), and treated with salbutamol after denervation (N = 30). Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21%) in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other beta2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.