The loss of skeletal muscle mass with aging has been attributed to a decline in muscle fiber number and muscle fiber size.
To define to what extent differences in leg muscle cross-sectional area ...(CSA) between young and elderly men are attributed to differences in muscle fiber size.
Quadriceps muscle CSA and type I and type II muscle fiber size were measured in healthy young (n=25; 23±1y) and older (n=26; 71±1y) men. Subsequently, the older subjects performed 6months of resistance type exercise training, after which measurements were repeated. Differences in quadriceps muscle CSA were compared with differences in type I and type II muscle fiber size.
Quadriceps CSA was substantially smaller in older versus young men (68±2 vs 80±2cm2, respectively; P<0.001). Type II muscle fiber size was substantially smaller in the elderly vs the young (29%; P<0.001), with a tendency of smaller type I muscle fibers (P=0.052). Differences in type II muscle fiber size fully explained differences in quadriceps CSA between groups. Prolonged resistance type exercise training in the elderly increased type II muscle fiber size by 24±8% (P<0.01), explaining 100±3% of the increase in quadriceps muscle CSA (from 68±2 to 74±2cm2).
Reduced muscle mass with aging is mainly attributed to smaller type II muscle fiber size and, as such, is unlikely accompanied by substantial muscle fiber loss. In line, the increase in muscle mass following prolonged resistance type exercise training can be attributed entirely to specific type II muscle fiber hypertrophy.
► Age-related differences in muscle size can be attributed to smaller muscle fibers. ► Training-induced increase in muscle size is attributed to muscle fiber hypertrophy. ► Large in muscle fiber numbers changes in aging or after training are unlikely. ► Interventions for sarcopenia should target type II muscle fiber hypertrophy.
Muscle wasting occurs in a variety of conditions, including both genetic diseases, such as muscular dystrophies, and acquired disorders, ranging from muscle disuse to cancer cachexia, from heart ...failure to aging sarcopenia. In most of these conditions, the loss of muscle tissue is not homogeneous, but involves specific muscle groups, for example Duchenne muscular dystrophy affects most body muscles but spares extraocular muscles, and other dystrophies affect selectively proximal or distal limb muscles. In addition, muscle atrophy can affect specific fiber types, involving predominantly slow type 1 or fast type 2 muscle fibers, and is frequently accompanied by a slow-to-fast or fast-to-slow fiber type shift. For example, muscle disuse, such as spinal cord injury, causes type 1 fiber atrophy with a slow-to-fast fiber type shift, whereas cancer cachexia leads to preferential atrophy of type 2 fibers with a fast-to-slow fiber type shift. The identification of the signaling pathways responsible for the differential response of muscles types and fiber types can lead to a better understanding of the pathogenesis of muscle wasting and to the design of therapeutic interventions appropriate for the specific disorders.
This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
To investigate the relationships between muscle fiber characteristics and meat quality traits of Korean native cattle, Hanwoo,
Longissimus dorsi (LD),
Psoas major (PM) and
Semimembranosus (SM) ...muscles obtained from 18 Hanwoo steers and the muscle fiber characteristics were measured by histochemical analysis. Fiber number, area percentages and density of type IIA and IIB were lower in SM muscle, but higher in PM muscle than other muscles. LD muscle had higher pH
24h,
L
⁎ value and fat content whereas SM muscle had lower
L
⁎ value and fat content. The lowest WBSF with longer sarcomere length was observed in PM muscle, while SM muscle showed the highest WBSF with shorter sarcomere length. Consequently, the percentage of type I and IIB were highly correlated with meat quality traits and inversely correlated with fat content,
L
⁎ value and WBSF. Fiber number and area percentage of type I had a positive correlation with fat content and
L
⁎ value and a negative correlation with WBSF. These results suggest that Hanwoo steers had high marbling, more lightness and tenderness when the percentage of type I was high and the percentage of type IIB was low in muscle.
We had the unique opportunity to study the skeletal muscle characteristics, at the single fiber level, of a world champion sprint runner who is the current indoor world record holder in the 60-m ...hurdles (7.30 s) and former world record holder in 110-m hurdles (12.91 s). Muscle biopsies were obtained from the vastus lateralis at rest and 4 h after a high-intensity exercise challenge (4 × 7 repetitions of resistance exercise). Single muscle fiber analyses were conducted for fiber type distribution (myosin heavy chain, MHC), fiber size, contractile function (strength, speed, and power) and mRNA expression (before and after the exercise bout). The world-class sprinter's leg muscle had a high abundance (24%) of the pure MHC IIx muscle fibers with a total fast-twitch fiber population of 71%. Power output of the MHC IIx fibers (35.1 ± 1.4 W/l) was 2-fold higher than MHC IIa fibers (17.1 ± 0.5 W/l) and 14-fold greater than MHC I fibers (2.5 ± 0.1 W/l). Additionally, the MHC IIx fibers were highly responsive to intense exercise at the transcriptional level for genes involved with muscle growth and remodeling (Fn14 and myostatin). To our knowledge, the abundance of pure MHC IIx muscle fibers is the highest observed in an elite sprinter. Further, the power output of the MHC IIa and MHC IIx muscle fibers was greater than any human values reported to date. These data provide a myocellular basis for the high level of sprinting success achieved by this individual.
Reduced mechanical loading during bedrest, spaceflight, and casting, causes rapid morphological changes in skeletal muscle: fiber atrophy and reduction of slow-twitch fibers. An emerging signaling ...event in response to unloading is the translocation of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma to the cytosol. We used EUK-134, a cell-permeable mimetic of superoxide dismutase and catalase, to test the role of redox signaling in nNOSμ translocation and muscle fiber atrophy as a result of short-term (54 h) hindlimb unloading. Fischer-344 rats were divided into ambulatory control, hindlimb-unloaded (HU), and hindlimb-unloaded + EUK-134 (HU-EUK) groups. EUK-134 mitigated the unloading-induced phenotype, including muscle fiber atrophy and muscle fiber-type shift from slow to fast. nNOSμ immunolocalization at the sarcolemma of the soleus was reduced with HU, while nNOSμ protein content in the cytosol increased with unloading. Translocation of nNOS from the sarcolemma to cytosol was virtually abolished by EUK-134. EUK-134 also mitigated dephosphorylation at Thr-32 of FoxO3a during HU. Hindlimb unloading elevated oxidative stress (4-hydroxynonenal) and increased sarcolemmal localization of Nox2 subunits gp91phox (Nox2) and p47phox, effects normalized by EUK-134. Thus, our findings are consistent with the hypothesis that oxidative stress triggers nNOSμ translocation from the sarcolemma and FoxO3a dephosphorylation as an early event during mechanical unloading. Thus, redox signaling may serve as a biological switch for nNOS to initiate morphological changes in skeletal muscle fibers.
Département d'Education Physique et de Réadaptation, Faculté de Médecine, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
Submitted 23 August 2005
; accepted in final form 24 November ...2005
Functional performance of lower limb muscles and contractile properties of chemically skinned single muscle fibers were evaluated before and after 8 wk of maximal effort stretch-shortening cycle (SSC) exercise training. Muscle biopsies were obtained from the vastus lateralis of eight men before and after the training period. Fibers were evaluated regarding their mechanical properties and subsequently classified according to their myosin heavy chain content (SDS-PAGE). After training, maximal leg extensor muscle force and vertical jump performance were improved 12% ( P < 0.01) and 13% ( P < 0.001), respectively. Single-fiber cross-sectional area increased 23% in type I ( P < 0.01), 22% in type IIa ( P < 0.001), and 30% in type IIa/IIx fibers ( P < 0.001). Peak force increased 19% in type I ( P < 0.01), 15% in type IIa ( P < 0.001), and 16% in type IIa/IIx fibers ( P < 0.001). When peak force was normalized with cross-sectional area, no changes were found for any fiber type. Maximal shortening velocity was increased 18, 29, and 22% in type I, IIa, and hybrid IIa/IIx fibers, respectively ( P < 0.001). Peak power was enhanced in all fiber types, and normalized peak power improved 9% in type IIa fibers ( P < 0.05). Fiber tension on passive stretch increased in IIa/IIx fibers only ( P < 0.05). In conclusion, short-term SSC exercise training enhanced single-fiber contraction performance via force and contraction velocity in type I, IIa, and IIa/IIx fibers. These results suggest that SSC exercises are an effective training approach to improve fiber force, contraction velocity, and therefore power.
skinned fibers; fiber hypertrophy; plyometry; passive stretch
Address for reprint requests and other correspondence: D. Theisen, 1 Place P. de Coubertin, B-1348 Louvain-La-Neuve, Belgium (e-mail: daniel.theisen{at}edph.ucl.ac.be )
Context:
The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes.
Objective:
Our objective was ...to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition.
Design:
Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry.
Participants and Setting:
Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic.
Main Outcome Measures:
Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated.
Results:
There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects.
Conclusion:
Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects.
Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid ...hormone receptor signaling in muscle to whole‐body energy metabolism and body temperature has not been resolved. Here, we show that T3‐induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1) in skeletal muscle, but that T3‐mediated elevation in body temperature is achieved in the absence of muscle‐TRα1. In slow‐twitch soleus muscle, loss‐of‐function of TRα1 (TRαHSACre) alters the fiber‐type composition toward a more oxidative phenotype. The change in fiber‐type composition, however, does not influence the running capacity or motivation to run. RNA‐sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1‐linked control of whole‐body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3‐stimulated increase in whole‐body energy expenditure.
Sarcopenia is a musculoskeletal disease that reduces muscle mass and strength in older individuals. The study investigates the effects of azilsartan (AZL) on skeletal muscle loss in natural ...sarcopenic rats. Male Sprague-Dawley rats aged 4-6 months and 18-21 months were selected as young-matched control and natural-aged (sarcopenic) rats, respectively. Rats were allocated into young and old control (YC and OC) and young and old AZL treatment (YT and OT) groups, which received vehicles and AZL (8 mg/kg, orally) for 6 weeks. Rats were then sacrificed after muscle function analysis. Serum and gastrocnemius (GN) muscles were isolated for further endpoints. AZL significantly improved muscle grip strength and antioxidant levels in sarcopenic rats. AZL also restored the levels of insulin, testosterone, and muscle biomarkers such as myostatin and creatinine kinase in sarcopenic rats. Furthermore, AZL treatment improved the cellular and ultrastructure of GN muscle and prevented the shift of type II (glycolytic) myofibers to type I (oxidative) myofibers. The results showed that AZL intervention restored protein synthesis in natural sarcopenic rats by increasing p-Akt-1 and decreasing muscle RING-finger protein-1 and tumor necrosis factor alpha immunoexpressions. In conclusion, the present findings showed that AZL could be an effective intervention in treating age-related muscle impairments.
Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple ...fiber types, but exercise's effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-
Hglucose (2-
HDG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-
HDG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.
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