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PubMed1979

The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. A protein-chemical analysis of muscle actin differentiation.

Complete amino acid sequences for four mammalian muscle actins are reported: bovine skeletal muscle actin, bovine cardiac actin, the major component of bovine aorta actin, and rabbit slow skeletal muscle actin. The number of different actins in a higher mammal for which full amino acid sequences are now available is therefore increased from two to five. Screening of different smooth muscle tissues revealed in addition to the aorta type actin a second smooth muscle actin, which appears very similar if not identical to chicken gizzard actin. Since the sequence of chicken gizzard actin is known, six different actins are presently characterized in a higher mammal. The two smooth muscle actins--bovine aorta actin and chicken gizzard actin--differ by only three amino acid substitutions, all located in the amino-terminal end. In the rest of their sequences both smooth muscle actins share the same four amino acid substitutions, which distinguish them from skeletal muscle actin. Cardiac muscle actin differs from skeletal muscle actin by only four amino acid exchanges. No amino acid substitutions were found when actins from rabbit fast and slow skeletal muscle were compared. In addition we summarize the amino acid substitution patterns of the six different mammalian actins and discuss their tissue specificity. The results show a very close relationship between the four muscle actins in comparison to the nonmuscle actins. The amino substitution patterns indicate that skeletal muscle actin is the highest differentiated actin form, whereas smooth muscle actins show a noticeably cloer relation to nonmuscle actins. By these criteria cardiac muscle actin lies between skeletal muscle actin and smooth muscle actins.

Actins↗

PubMed1978

[Contractile properties of the striated muscle fibres of esophageal muscle in comparison with skeletal muscle in rats].

The contractile properties of the striated oesophageal muscle of the rat were studied in vitro at 35 degrees C and 25 degrees C. They were compared with those of the slow-twitch soleus muscle and the fast-twitch extensor digitorum longus (EDL) muscle of the same animals. The contraction time of the oesophageal muscle is 30 msec (+/- 2.5 msec S.E.) at 35 degrees C. It is little but significantly longer than those of the soleus muscle. It is remarkable that the twitch-tetanus ratio of the oesophageal muscle fibres is approximately twice that of the skeletal muscles. Immediately after a tetanic stimulation the amplitude of a single twitch of the fast EDL is increased (posttetanic potentiation); in the slow soleus muscle it is unchanged or decreased, however. Also the muscle fibres of the oesophagus exhibit a post-tetanic-potentiation, but this is smaller than in EDL. A decrease of the temperature of the bathing solution causes in preparations of the fast EDL a higher tension developed by a single twitch (cold potentiation). This is not detectable in preparations of the slow soleus muscle. The oesophageal muscle shows also a remarkable cold potentiation, but it is smaller than in EDL. An increase of the extracellular K+-concentration evokes a short-lasting contracture in the investigated rat muscles. The mechanical thresholds of the oesophageal muscle fibres are clearly higher than those of the soleus muscle but lower than those of the EDL. The striated oesophageal muscle fibres of the rat in spite of their low speed of contraction show some properties of muscle fibres of the fast twitch type.

Animals↗

PubMed2025

Impact of Muscle Quality on Muscle Strength and Physical Performance Beyond Muscle Mass or Diabetes Status.

BACKGROUND: Muscle quality, represented by myosteatosis, is recognized as an important factor in sarcopenia. In this study, we aimed to determine the associations between myosteatosis, muscle strength and physical performance among the elderly South Korean population. METHODS: We included 1440 participants (mean age 62.7 ± 6.2 years) from the Korean Genome and Epidemiology Study (KoGES). Based on the computed tomography attenuation of mid-thigh imaging, the total muscle area (TMA), normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA) and inter-intramuscular adipose tissue (IMAT) and its indices were used to evaluate myosteatosis. Muscle strength was evaluated using hand grip strength, whereas physical performance was evaluated through 4-m gait speed, a 30-s sit-to-stand test and 2-min walking test. RESULTS: Of the 1440 patients, 51.5% were women, and 37.2% had diabetes. With aging, the LAMA index gradually increased, and the NAMA index gradually decreased in both men and women (p for trend < 0.001). The NAMA index was positively associated, whereas the LAMA and IMAT indices were negatively associated with muscle strength and physical performance after adjusting for age and sex. Higher tertiles of the NAMA index were consistently associated with improved physical performance across all appendicular skeletal muscle tertiles. The relationship between the NAMA index or LAMA index and muscle strength and physical performance did not differ according to diabetic status. Regular exercise was associated with a higher NAMA index and a lower LAMA index in the non-diabetic group; however, no significant difference in muscle quality was observed in the diabetic group in relation to exercise. CONCLUSIONS: Reduced myosteatosis was positively associated with greater muscle strength and better physical performance in both men and women, regardless of muscle mass or diabetes status; improving myosteatosis may be a therapeutic target for the prevention of sarcopenia.

Humans↗

PubMedDate not supplied

Fine structure of muscle in human disuse atrophy: significance of proximal muscle involvement in muscle disorders.

The universal occurrence of weakness of skeletal musculature on disuse, however produced, and the paucity of published reports on the fine structural changes in human disuse atrophy, prompted the present investigation. The quadriceps muscle of a leg immobilized in plaster cast (for fracture) and of the opposite non-immobilized limb was biopsied in four adult males, after periods of immobilization from 50 to 75 days. These 8 muscle specimens were examined for histopathological changes, and muscle fibre diameters were measured by micrometry from paraffin sections. The histograms revealed a larger proportion of small fibres (less than 20 micron) and a smaller proportion of large fibres (greater than 40 micron) in the immobilized limb compared to the opposite. Thus, light microscopy showed only atrophic changes. This was confirmed by electronmicroscopy, where atrophy of few to several muscle fibres was seen in the form of loss of myofibrils, collapse and folding of the basement membrane and prominence of glycogen or muscle nuclei. The atrophic change was more severe in the immobilized limbs, but it was also noticeable in all the non-immobilized limbs. Degenerative changes, especially disorganization and breakdown of myofibrils, and fragmentation of plasma membrane, were also seen in occasional atrophied muscle fibres, again more frequently in the immobilized limb. Lipofuscin was often found accumulated in muscle fibres and occasionally in endothelial cells of intramuscular blood vessels; the latter showed prominent pinocytotic vesicles or thickened basement membrane. It is concluded that both atrophy and degeneration of fibres of proximal muscles can occur as non-specific consequences of disuse of the limb in man, that degeneration is a latter and more severe change, that muscles even of the non-immobilized leg are subjected to disuse atrophy during bed-rest, and that the proximal muscles in man seem to have a natural susceptibility to atrophy and degeneration in any muscular disorders.

Adult↗

PubMed2026

Skeletal Muscles Do Not Compete for Growth: Activating Additional Muscle Mass Does Not Compromise Changes in Muscle Size.

Kataoka, R, Yamada, Y, Hammert, WB, Sallberg, RW, Kang, A, Song, JS, Kassiano, W, Metcalf, EE, and Loenneke, JP. Skeletal muscles do not compete for growth: Activating additional muscle mass does not compromise changes in muscle size. J Strength Cond Res 40(9): 1043-1049, 2026-This study investigated whether the magnitude of muscle size and strength differed based on the amount of muscle recruited during training sessions. One hundred five untrained individuals were randomly assigned to 1 of 3 groups: low-load unilateral elbow flexion exercise (a) to failure (LL-Failure, n = 36), (b) to failure and low-load knee extension exercise to failure (LL-Failure + Legs, n = 33), or (c) a time-matched nonexercise control (CON, n = 36). Training groups completed 18 supervised sessions over 6 weeks (2 sets at 30% 1 repetition maximum [1RM] to failure). LL-Failure + Legs group performed 4 additional sets of knee extension exercise in each leg (20-30 RM). Muscle thickness on the anterior upper arm (60 and 70% sites) and elbow flexor 1RM strength of the trained arm were measured at pretesting and posttesting. Changes were compared using the ANCOVA function of Bayes Factors for Informative Hypotheses (prevalues as the covariate). Specific hypotheses were evaluated by comparing Bayes factors and the posterior probabilities between models. Six weeks of training led to increases in muscle size and strength. However, performing additional leg exercise did not attenuate the muscle growth in the anterior upper arm (0.19 cm) compared with performing only arm exercise to failure (0.18 cm). Changes in 1RM strength also did not differ between training groups (0.32 and 0.25 kg for LL-Failure and LL-Failure + Legs, respectively). Overall, there was no evidence for competition of adaptations in muscle size and strength under uncontrolled nutritional conditions. Whether greater training volume or limited nutrient intake induces a competition for resources warrants further investigation.

Humans↗

PubMedDate not supplied

Turnover rates of muscle proteins in cardiac, skeletal, and smooth muscle: turnover rate related to muscle function.

The turnover rate of muscle proteins was related to the physiological function of the muscle in dogs, fowl, rats, and mice. The turnover rates of mixed muscle proteins were most rapid in cardiac muscle, intermediate in red tonic and mixed fiber-type muscles, and slowest in white twitch skeletal muscle. This same progression in turnover rates also was shown in the subcellular fractions of muscle-sarcoplasmic and myofibrillar proteins-as well as in purified proteins, myosin, and tropomyosin. The RNA concentration of muscle was highly correlated with the protein turnover rate, and the RNA activity, i.e., the translational efficiency of the RNA, was similar in the different muscle types.

Animals↗

PubMed1978

Turnover rates of muscle protein in cardiac and skeletal muscles of dog, fowl, rat and mouse: turnover rate related to muscle function.

Turnover rates of muscle protein in cardiac and skeletal muscle have been measured in dogs using a continuous infusion of 14C-tyrosine, and in fowls, rats and mice after a pulse label of either 3H-leucine or 3H-aspartate. In all species the total mixed protein from ventricle turned over the most rapidly. Tonic muscles predominantly comprised of red fibres were intermediate in rate and twitch muscles comprised of predominantly white fibres had the slowest rates of turnover. This same progression of turnover rates was also seen in myofibrillar and sarcoplasmic protein fractions and with myosin. The RNA concentrations of the muscle tissue were highly correlated with the turnover rates. It is suggested that the turnover rate of muscle protein is related to the function of the muscle.

Animals↗

PubMed1979

Extended amino acid sequences around the active-site lysine residue of class-I fructose 1,6-bisphosphate aldolases from rabbit muscle, sturgeon muscle, trout muscle and ox liver.

1. Amino acid sequences covering the region between residues 173 and 248 [adopting the numbering system proposed by Lai, Nakai & Chang (1974) Science 183, 1204-1206] were derived for trout (Salmo trutta) muscle aldolase and for ox liver aldolase. A comparable sequence was derived for residues 180-248 of sturgeon (Acipenser transmontanus) muscle aldolase. The close homology with the rabbit muscle enzyme was used to align the peptides of the other aldolases from which the sequences were derived. The results also allowed a partial sequence for the N-terminal 39 residues for the ox liver enzyme to be deduced. 2. In the light of the strong homology evinced for these enzymes, a re-investigation of the amino acid sequence of rabbit muscle aldolase between residues 181 and 185 was undertaken. This indicated the presence of a hitherto unsuspected -Ile-Val-sequence between residues 181 and 182 and the need to invert the sequence -Glu-Val- to -Val-Glx- at positions 184 and 185. 3. Comparison of the available amino acid sequences of these enzymes suggested an early evolutionary divergence of the genes for muscle and liver aldolases. It was also consistent with other evidence that the central region of the primary structure of these enzymes (which includes the active-site lysine-227) forms part of a conserved folding domain in the protein subunit. 4. Detailed evidence for the amino acid sequences proposed has been deposited as Suy Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.

Amino Acid Sequence↗

PubMed1978

A comparative study of the myosin light chain kinases from myoblast and muscle sources. Studies on the kinases from proliferative rat myoblasts in culture, rat thigh muscle, and rabbit skeletal muscle.

Myosin light chain kinases have been isolated from rat thigh and rabbit skeletal muscle and cultured rat myoblasts. From these preparations, two types of kinases can be distinguished: calcium-dependent and calcium-independent. Both types of kinases can phosphorylate isolated P-light chains of myosin from several sources (skeletal muscle, cardiac muscle, and platelet). Data are shown which support the phosphorylation of the same site on the non-muscle P-light chains by both types of kinases. The rates of these reactins are, however, different for the two types of kinases. Kinetic analysis of the myoblast kinase shows differing affinities for various P-light chains (non-muscle greater than cardiac greater than skeletal). In the proliferative rat myoblast, phosphorylation of myosin is a prerequisite for actin activation of the myosin ATPase activity.

Adenosine Triphosphatases↗

PubMed1978

Effect of diazepam on the gamma motor system indicated by the responses of the muscle spindle of the triceps surae muscle of the decerebrate cat to the muscle stretch.

The experiments were performed on 37 intercollicularly decerebrate cats. The triceps surae muscle was subjected to trapezoidal stretches of 10 mm/s or 2 mm/s over a length of 14 mm. The reflex arc was left partially or fully intact. The effect of diazepam given intravenously on the discharge frequencies of group Ia afferent fibres from muscle spindles in the belly of the triceps surae muscle was studied. Diazepam depressed both the dynamic and the static gamma motor responses. When gamma motor fibres were selectively blocked by procaine a parallel shift of the tension-extension curve was observed. From comparison of the effect of procaine and diazepam on the phasic and static responses of the muscle spindle it was concluded that directly after the injection of diazepam the gamma motor activity was completely abolished at a dose as low as 0.1 mg/kg whereas the alpha motor system was only partly depressed even at higher doses. Differences in the effect of diazepam on the dynamic and static gamma system respectively, could not be found.

Action Potentials↗

PubMed1979

[Spasm of the adductor muscles, pre-dislocation and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part I: The effect of open myotenotomy of the gracilis muscle and of the long and short adductor muscles in connection with total extrapelvine resection of the obturator nerve, on the hip joints and static function (author's transl)].

Spasm and contraction of the adductor muscles involve, on the one hand, danger in respect of the development of a dislocation of the hip, and are a serious impediment to a walking ability on the other. Hence, surgery is often necessary. The article reports on the results of consequent weakening of the adductor muscles as a result of open myotenotomy in association with complete extrapelvine resection of the obturator nerve. 27 patients were subjected to surgery--in most cases bilaterally--at an age between 2 years and 5 months and 18 years, with a follow-up period of up to 15 years. The study does not include patients with spastic dislocation of the hip in whom this method was applied on the non-dislocated side and on the dislocated side in combination with iliopsoas tenotomy. This method makes it possible to achieve regression of existing defective positions of the hip joints. In a few cases, the valgus position of the neck of the femur was corrected to some extent. In two patients it was not possible to prevent the progress of a developing dislocation of the hip. These results show that, whereas the adductor muscles represent an essential factor for the occurrence of a spastic dislocation of the hip, other forces are most probably also involved. In the majority of cases, results were favourable in respect of the static function, although in some cases the success became evident after several years only, especially in mentally retarded patients and in apathetic individuals. Important for therapeutic success is the follow-up. The principles of its therapy are thoroughly discussed. Surgery is indicated only in special cases. Indications must be observed very strictly, since the risk of excessive weakening of the adductor muscles should not be underestimated.

Adolescent↗

PubMed1978

[The organogenic development of the human peroneal muscle of the IVth digit from the peroneal muscle of the Vth digit and the short peroneal muscle from the viewpoint of evolutive myology].

The preliminary author's investigations revealed, that the mm. peronei digitorum group in Mammalia (including Man) underwent its own morphological evolution. The author failed to establish the facts that indicated the homology between the above mentioned muscles and m. extensor digitorum brevis. But, at present due to the lack of detailed determinations of organogenesis of mm. peronei digitorum and of m. peroneus brevis, it was not possible to prove the above mentioned indications. The observations on organogenesis of the respective muscles, carried out at present upon 13 human embryos with 12 to 32 mm crown-rump length and 5 fetuses with 35 to 65 mm crown-rump length, revealed that, mm. peronei digitorum primordium initiated its development as a muscle of two fingers (m. peroneus digiti IV. et m. peroneus digiti V), passed through its one-finger form (m. peroneus digiti V) and usually terminated with its complete reduction.

Biological Evolution↗

PubMed1979

Influence of muscle temperature on maximal muscle strength and power output in human skeletal muscles.

The influence of muscle temperature (Tm) on maximal muscle strength, power output, jumping, and sprinting performance was evaluated in four male subjects. In one of the subjects the electromyogram (EMG) was recorded from M. vastus lateralis, M. biceps femoris, and M. semitendinosus. Tm ranged from 30.0 degrees C to 39 degrees C. Maximal dynamic strength, power output, jumping, and sprinting performance were positively related to Tm. The changes were in the same order of magnitude for all these parameters (4-6% x degrees C-1) Maximal isometric strength decreased by 2% x degrees C-1 with decreasing Tm. The force-velocity relationship was shifted to the left at subnormal Tm. Thus in short term exercises, such as jumping and sprinting, performance is reduced at low Tm and enhanced at Tm above normal, primarily as a result of a variation in maximal dynamic strength.

Adult↗

PubMed1978

The properties of the extraocular muscles of the frog. I. Mechanical properties of the isolated superior oblique and superior rectus muscles.

The mechanical properties of two extraocular muscles (superior oblique and superior rectus muscles) of the frog were studied and compared with those of a frog's skeletal muscle (iliofibularis muscle) which contains the same types of muscle fibres as the oculorotatory muscles. The extraocular muscles are very fast twitching muscles. They exhibit a smaller contraction time, a smaller half-relaxation time, a higher fusion frequency, and a lower twitch-tetanus ratio than the skeletal muscles. The maximum isometric tetanic tension produced per unit cross-sectional area is lower in the extraocular muscles than in skeletal muscles. However, the extraocular muscles show a higher fatigue resistance than the skeletal muscles. With respect to the dynamic properties there are some differences between the various oculorotatory muscles of the frog. The superior rectus muscle exhibits a faster time-course of the contraction, a higher fusion frequency, and a higher fatigability than the superior oblique muscle. An increase of the extracellular K+-concentration evokes sustained contractures not only in the extraocular muscles but also in the iliofibularis muscle; between these muscles there are no striking differences in the mechanical threshold of the whole muscle preparation. The mechanical threshold depends on the Ca++-concentration of the bathing solution and it is found in a range between 12.5 and 17.5 mM K+ in a normal Ringer solution containing 1.8 mM Ca++. The static-mechanical properties of the extraocular muscles of the frog and the dependence of the active developed tension on the muscle extension are very similar to those which are known to exist in the extraocular muscles of other vertebrates. In tetanic activated frog's oculorotatory muscles a linear relationship exists between length and tension. A variation of the stimulation frequency does not change the slope of this curve but causes parallel shifts of the curve. The peculiar properties of the extraocular muscles of the frog are discussed with respect to the muscle fibre types in these muscles and to the diameter of the muscle fibres.

Animals↗

PubMedDate not supplied

Muscle trophic factor: I. Assay of a muscle trophic factor by measurement of muscle cell nuclei.

A method for assaying a skeletal muscle cell trophic factor in chicken serum is described. The number of myoblast and myotube nuclei was considered to reflect the rate of myoblast multiplication and was thus adopted as an index for the activity of the trophic factor. In a 35-mm Falcon plastic Petri dish, 2.5 x 10(40) to 10(5) myoblasts were cultured. The culture medium consisted of 85% Eagle's minimum essential medium and 15% horse serum. The assay medium was composed of 2.4 ml of this culture medium and 0.1 ml of partially purified trophic factor or appropriately diluted chicken serum. Four dishes were prepared for each sample under identical conditions. On day 4 of incubation, cells were fixed, stained and observed under a microscope, and the number of nuclei in 20 fields was counted. The mean number of nuclei obtained from the four dishes was used to denote a single point. A three-point common-zero method of slope-ratio assay was used to calculate activity. The activity of the trophic factor was expressed with reference to the effect of the control serum on myoblast multiplication.

Animals↗

PubMed1979

Neural control of skeletal muscle cholinesterase: a study using organ-cultured rat muscle.

1. It has been proposed that the influence of innervation on the cholinesterase activity (ChE) of skeletal muscle and on end-plate ChE in particular is mediated by trophic substance(s) moved by axonal transport and released from nerve. We have tested this hypothesis using rat extensor digitorum longus (e.d.l.) and diaphragm muscles denervated in vitro for several days and then maintained in organ culture to assay putative trophic substance(s). 2. The cholinesterase activity (ChE) of rat extensor digitorum longus (e.d.l.) muscles decreased dramatically after 5 days of denervation in vivo as previously reported. The ChE of rat e.d.l. muscles denervated in vivo for 3 days and then maintained in organ culture for 2 days was essentially identical to that of muscles denervated 5 days in vivo. 3. The ChE OF E.D.L. MUSCLES DENERVATED IN VIVO FOR 3 DAYS AND THEN MAINTAINED FOR 2 DAYS IN CULTURE MEDIUM SUPPLEMENTED WITH SCIATIC NERVE OR INNERVATED MUSCLE EXTRACT WAS SIGNIFICANTLY HIGHER THAN THAT OF MUSCLES DENERVATED IN VIVO FOR 5 DAYS OR DENERVATED IN VIVO FOR 3 DAYS AND THEN CULTURED FOR 2 DAYS IN CULTURE MEDIUM ALONE. Supplementing the culture medium with brain or spinal cord extract also significantly increased the ChE of organ-cultured e.d.l. muscles. 4. Supplementing the culture medium with liver or spleen extract or with the extract of muscle denervated for 3--7 days in vivo before extraction did not increase the ChE or organ-cultured e.d.l. muscles. 5. The effect of muscle extract on the ChE of organ-cultured e.d.l. muscles was dose dependent and occurred gradually reaching a maximum after approximately 24 h of culture. 6. Substance(s) which increased the ChE of organ-cultured e.d.l. muscles were found to accumulate in transected sciatic nerve in the region just proximal to the site of transection where substances moved by axonal transport are known to accumulate. 7. Media conditioned with neurally stimulated e.d.l. or diaphragm muscles caused a substantial and highly significant increase in the ChE of e.d.l. or diaphragm muscles denervated in vivo and then maintained in organ culture. Media conditioned in the same way with unstimulated muscles did not increase the ChE OF ORGAN-CULTURED MUSCLES. 8. The active substance(s) released by neural stimulation continued to be released when muscle contraction was blocked by adding D-tubocurarine to the medium during conditioning but the release of these substance(s) was significantly reduced when magnesium (10mM) was added to the medium during conditioning. 9 The substance(s) released by neural stimulation selectively increased ChE in the end-plate region. In diaphragm segments denervated in vivo and then maintained in medium conditioned with neurally stimulated muscle, there was a 102% increase in end-plate ChE but no detectable increase in background ChE. 10...

Animals↗

PubMed2026

Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio-adipose-muscle axis.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood. METHODS: We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction. RESULTS: Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty. CONCLUSIONS: Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress-muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio-adipose-muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.

Humans↗

PubMed2025

Genome-Wide Association Study on Muscle Stiffness Identified Novel Locus for Predisposition to Muscle Strain Injury.

PURPOSE: We aimed to screen the entire genome for genetic variants associated with passive muscle stiffness, which has been suggested as a risk factor for muscle strain injury. METHODS: This genome-wide association study (GWAS) on passive muscle stiffness included 350 physically active young Japanese individuals. Three hamstring constituents were measured using ultrasound shear wave elastography. Skeletal muscle transcriptomes were compared across the genotypes of GWAS-identified variants in 48 healthy Japanese individuals. Association between GWAS-identified variants and history of muscle strain injury was examined in 1428 Japanese athletes. RESULTS: Two loci on chromosome 11 demonstrated a genome-wide significant association with passive muscle stiffness of the biceps femoris long head (rs12807854 T/C: P = 5.19 × 10 -10 , rs78405694 T/C: P = 2.09 × 10 -8 ; linear regression analysis adjusted for sex, age, and stretching exercise habits). Skeletal muscle RNA sequencing revealed significantly elevated expression of extracellular matrix-related genes in muscles carrying stiffness-increasing alleles of these variants. Among athletes, rs12807854 T/C was significantly associated with a history of muscle strain injury ( P = 0.0254; logistic regression analysis adjusted for age, sex, competitive level, and main sport). Carriers of the C allele, associated with increased muscle stiffness, exhibited a heightened risk of muscle strain injury (odds ratio = 1.62; 95% confidence interval = 1.06-2.47 per C allele increase). By contrast, rs78405694 did not show a significant association with muscle strain injury in this population. CONCLUSIONS: A novel locus associated with passive muscle stiffness and muscle strain injury was identified. Elucidating the detailed mechanisms linking the identified locus to passive muscle stiffness may lead to the development of new strategies to prevent muscle strain injuries.

Humans↗