Decline In Muscle Performance Research Articles

Clinical benefit of botulinum toxin for treatment of persistent TMD-related myofascial pain: A randomized, placebo-controlled, cross-over trial.

Injections of botulinum toxin type A (BoNT-A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)-related myofascial pain (MFP). BoNT-A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo-controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT-A. Sixty-six subjects were randomized into two groups, one which received BoNT-A first and a second which received a saline solution (SS) first. Follow-ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain-related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated. The within-group analysis showed a significant improvement in pain intensity and pain-related disability after BoNT-A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between-group analysis of pain-related variables revealed no differences between groups at any time. Nonetheless, BoNT-A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16-week follow-ups favoring BoNT-A. Injections of 50 U of BoNT-A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious.

Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis

PurposeMitofusin 2 (Mfn2) is one of two mitofusins involved in regulating mitochondrial size, shape and function, including mitophagy, an important cellular mechanism to limit oxidative stress. Reduced expression of Mfn2 has been associated with impaired osteoblast differentiation and function and a reduction in the number of viable osteocytes in bone. We hypothesized that the genetic absence of Mfn2 in these cells would increase their susceptibility to aging-associated metabolic stress, leading to a progressive impairment in skeletal homeostasis over time. MethodsMfn2 was selectively deleted in vivo at three different stages of osteoblast lineage commitment by crossing mice in which the Mfn2 gene was floxed with transgenic mice expressing Cre under the control of the promoter for Osterix (OSX), collagen1a1, or DMP1 (Dentin Matrix Acidic Phosphoprotein 1). ResultsMice in which Mfn2 was deleted using DMP1-cre demonstrated a progressive and dramatic decline in bone mineral density (BMD) beginning at 10 weeks of age (n = 5 for each sex and each genotype from age 10 to 20 weeks). By 15 weeks, there was evidence for a functional decline in muscle performance as assessed using a rotarod apparatus (n = 3; 2 males/ 1 female for each genotype), accompanied by a decline in lean body mass. A marked reduction in trabecular bone mass was evident on bone histomorphometry, and biomechanical testing at 25 weeks (k/o: 2 male/1 female, control 2 male/2 female) revealed severely impaired femur strength. Extensive regional myofiber atrophy and degeneration was observed on skeletal muscle histology. Electron microscopy showed progressive disruption of cellular architecture, with disorganized sarcomeres and a bloated mitochondrial reticulum. There was also evidence of neurodegeneration within the ventral horn and roots of the lumbar spinal cord, which was accompanied by myelin loss and myofiber atrophy. Deletion of Mfn2 using OSX-cre or Col1a1-cre did not result in a musculoskeletal phenotype. Where possible, male and female animals were analyzed separately, but small numbers of animals in each group limited statistical power. For other outcomes, where sex was not considered, small sample sizes might still limit the strength of the observation. ConclusionDespite known functional overlap of Mfn1 and Mfn2 in some tissues, and their co-expression in bone, muscle and spinal cord, deletion of Mfn2 using the 8 kB DMP1 promoter uncovered an important non-redundant role for Mfn2 in maintaining the neuromuscular/bone axis.

Circulating Neurofilament Light Chain Levels Increase with Age and Are Associated with Worse Physical Function and Body Composition in Men but Not in Women.

This study aimed to assess the relationship between age-related changes in Neurofilament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. The study included 40 participants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of muscle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analysis revealed significant associations between NFL levels and specific metabolites, with gender-dependent relationships observed. This study provides insights into the relationship between circulating serum NFL, muscle function, and aging. Our findings hint at circulating NFL as a potential early marker of age-associated neurodegenerative processes, especially in men.

Lack of the myotendinous junction marker col22a1 results in posture and locomotion disabilities in zebrafish

The myotendinous junction (MTJ) is essential for the integrity of the musculoskeletal unit. Here, we show that gene ablation of the MTJ marker col22a1 in zebrafish results in MTJ dysfunction but with variable degrees of expression and distinct phenotypic classes. While most individuals reach adulthood with no overt muscle phenotype (class 1), a subset of the progeny displays severe movement impairment and die before metamorphosis (class 2). Yet all mutants display muscle weakness due to ineffective muscle force transmission that is ultimately detrimental for class-specific locomotion-related functions. Movement impairment at the critical stage of swimming postural learning causes class 2 larval death by compromising food intake. In class 1 adults, intensive exercise is required to uncover a decline in muscle performance, accompanied by higher energy demand and mitochondrial adaptation. This study underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.

Age-related biochemical and histological changes in the soleus muscle of male mice

During aging, skeletal muscle is subjected to progressiveloss of muscle mass and strength (sarcopenia) and a decline in thefunctional ability. The reduction in the antioxidative capacity ofthe skeletal muscle resulting in an abnormal accumulation of thereactive oxygen species (ROS) that is one of the possible causesof the decline in muscle performance. In this study thehistological changes in the soleus muscles of male mice at the ageof 1st and 15th old were examined and the activities of theantioxidant enzymes, CAT and SOD, non- enzymatic antioxidantGPH and MDA level were measured to clarify the age-relatedchanges in healthy subjects. Results showed that there is asignificant reduction (P ≤ 0.05) in the antioxidants SOD, CATand GPH and there is a significant increase (P ≤ 0.05) in MDAlevel at the age of 15th month when compared to 1st month old.We concluded that the activities of the antioxidants were affectedby aging. Moreover, there is age- related lipid peroxidation.

Association Between the Decline in Muscle Health and the Decline in Bone Health in Older Individuals from the SarcoPhAge Cohort.

The longitudinal relationship between bone health and muscle health is scarcely explored. We aimed to explore the relationship between bone decline and muscle decline over 1year in older individuals. We used data from the SarcoPhAge cohort, which aims to identify the consequences of sarcopenia. In this way, this study also highlights the yearly changes in muscle mass (by dual-energy absorptiometry), muscle weakness (by grip strength), and/or physical performance (by the short physical performance battery test). Measurements of areal bone mineral density (aBMD), enabling the diagnosis of osteoporosis, and bone microarchitecture (by means of the trabecular bone score) were also performed each year. A 1-year clinically relevant decline in bone and muscle health components was evidenced using the Edwards-Nunnally index. Among the 232 participants with complete data (75.5 ± 5.4years, 57.8% women), we observed an association between a clinically relevant decline in the skeletal muscle mass index (SMI) and a decrease in aBMD (adjusted OR = 2.12 [1.14-2.51] for the spine, 2.42 [1.10-5.34] for the hip and 2.12 [1.04-5.81] for the neck), as well as a significant association between SMI and deterioration of the skeletal microarchitecture (aOR = 3.99 [2.07-7.70]). A clinically relevant decline in muscle strength was associated with a decrease in spine aBMD (aOR = 2.93 [1.21-7.12]) and hip aBMD (aOR = 3.42 [1.37-7.64]) only. The decline in muscle performance was related to the decline in bone microarchitecture only (aOR = 2.52 [1.23-5.17]). Individuals with incident sarcopenia had an approximately fivefold higher risk of concomitantly developing osteoporosis. A dynamic relationship between impaired muscle and bone health was observed, with an obvious association between the concomitant incidences of osteoporosis and sarcopenia.

Do Older Adults Who Meet 2008 Physical Activity Guidelines Have Better Physical Performance Than Those Who Do Not Meet?

An observed consequence of aging is a decline in muscle performance that includes a loss in both muscle strength and muscle power. This decline can lead to loss of function and independence and is a predictor of disability in older adults. Although the 2008 Physical Activity (PA) Guidelines for Americans provides a guideline for muscle strengthening, there is no evidence that performing muscle strengthening 2 times a week for all major muscle groups is related to better performance on measures known to be important factors in development or progression of frailty in older adults. The purposes of this study were to assess muscle-strengthening and aerobic PA behaviors in older adults and to determine the relationship between the PA behaviors and physical performance measures. This was a cross-sectional study of 85 community-dwelling, ambulatory adults (50 women, 35 men) with a mean (standard deviation) age of 67.5 (5.6) years. All used an internet-based survey, TREST (Tracking Resistance Exercise and Strength Training), to report muscle-strengthening and aerobic PA behavior. Physical performance measures of grip strength, 10-m walk test (10-MWT), five-time sit-to-stand test (FTSST), and stair climb test (SCT) were obtained following completion of the survey. Participants were grouped by whether they met 2008 PA Guidelines for (1) muscle strengthening 2 or more days per week, (2) muscle strengthening 2 or more days per week using all major muscle groups, or (3) 150 minutes or more per week of aerobic moderate to vigorous physical activity. Comparisons of physical performance measures were conducted between participants who met and did not meet guidelines using multivariate analyses. Significant multivariate results were followed with one-tailed t tests. The participants meeting muscle strengthening 2 or more days per week performed significantly better on measures of grip strength and SCT. Only 27% of participants met the more stringent-strengthening guideline of 2 or more days per week using all major muscle groups, and these individuals performed significantly better on the SCT and FTSST. The participants meeting the aerobic activity guideline performed significantly better on the SCT, the FTSST, and the 10-MWT.However, participants who met both the strengthening and aerobic activity guidelines performed significantly better on all 4 physical performance measures than participants who met neither of the guidelines. Meeting guidelines for both aerobic and muscle-strengthening activities may be the most effective way of preserving muscle strength, muscle power, and gait velocity in older adults, but this conclusion must be tested with an intervention study.

Physical decline and survival in the elderly are affected by the genetic variability of amino acid transporter genes.

Amino acid (AA) availability is a rate-limiting factor in the regulation of muscle protein metabolism and, consequently, a risk factor for age-related decline in muscle performance. AA transporters are emerging as sensors of AA availability and activators of mTORC1 signalling, acting as transceptors. Here, we evaluated the association of 58 single nucleotide polymorphisms (SNPs) in 10 selected AA transporter genes with parameters of physical performance (Hand Grip, Activity of Daily Living, Walking time). By analysing a sample of 475 subjects aged 50-89 years, we found significant associations with SLC7A5/LAT1, SLC7A8/LAT2, SLC36A1/PAT1, SLC38A2/SNAT2, SLC3A2/CD98, SLC38A7/SNAT7 genes. Further investigation of the SNPs in a cross-sectional study including 290 subjects aged 90-107 years revealed associations of SLC3A2/CD98, SLC38A2/SNAT2, SLC38A3/SNAT3, SLC38A9/SNAT9 variability with longevity. Finally, a longitudinal study examining the survival rate over 10 years showed age-dependent complexity due to possible antagonistic pleiotropic effects for a SNP in SLC38A9/SNAT9, conferring a survival advantage before 90 years of age and a disadvantage later, probably due to the remodelling of AA metabolism. On the whole, our findings support the hypothesis that AA transporters may impact on the age-related physical decline and survival at old age in a complex way, likely through a mechanism involving mTORC1 signalling.

Stuck in gear: age-related loss of variable gearing in skeletal muscle.

Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (P<0.05) from 19.1±5.0 kPa and 188.5±24.2 MPa, respectively, in young rats to 39.1±4.2 kPa and 328.0±48.3 MPa in old rats, indicating a mechanical change in the interaction between contractile and connective tissues. Gear ratio decreased with increasing force in young (P<0.001) but not old (P=0.72) muscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age.

High-Speed Power Training Improves Arterial Compliance And Endothelial Function In Older Adults.

PURPOSE: After age 65 there is a steep decline in muscle performance and function, while at the same time cardiovascular disease (CVD) risk increases dramatically. Traditional slow-speed strength training (SSST) is regularly prescribed to help reverse age-related declines in muscle performance and function; however, compared to more moderate intensity resistance training, SSST may increase arterial stiffness, potentially exacerbating risk for CVD. High-speed power training (HSPT) is a low-to moderate intensity resistance training protocol that improves muscle performance and function as much, or more, than traditional SSST in older adults. The purpose of this study was to examine whether HSPT would be more beneficial to vascular health compared to SSST in older men and women. METHODS: For this pilot study, 7 community-dwelling men and women (4m, 3f; age: 71±2 years) were randomized into a 16-week lower extremity resistance training intervention of either HSPT (n=4; 3 x 12-14 repetitions at 40% of the one-repetition-maximum [1RM]) at high velocity) 3 x/week; or slow-speed strength training (SSST: n=3; 3 x 8-10 repetitions at 80%1RM at slow velocity) 3 x/week. Leg Press (LP) muscle strength, peak power and peak power velocity were obtained at 40%-90%1RM. Arterial compliance was measured in the femoral artery and endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery. RESULTS: HSPT improved muscle performance measures of 1RM strength, peak power and peak power velocity as much, or more, than traditional SSST in older adults. Muscle strength, peak power, and peak power velocity improved 11% (1838±483N to 2035±415N), 15% (1124±244W to 1298±288W), and 15% (1.06±0.07m/s to 1.22±0.14m/s) with HSPT, respectively, and 13% (1625±641N to 1835±768N), 9% (1024±527W to 1119±509W), and -1.5% (1.11±0.22m/s to 1.09±0.20m/s) with SSST, respectively. In terms of vascular measures, brachial FMD normalized to shear stimulus improved 35% (0.41 A.U. to 0.58 A.U.) following HSPT with no changes found after SSST. Likewise, femoral arterial compliance improved in HSPT (0.05 mm/mmHg to 0.1 mm/mmHg). CONCLUSIONS: These preliminary findings suggest that high-speed power training may confer vascular benefits that are not manifest following traditional slow-speed strength training.

Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism.

Accumulation of reactive oxygen species (ROS) in skeletal muscles and the resulting decline in muscle performance are hallmarks of sarcopenia. However, the precise mechanism by which ROS results in a decline in muscle performance is unclear. We demonstrate that isometric-exercise concomitantly increases the activities of Silent information regulator 1 (SIRT-1) and Poly [ADP-ribose] polymerase (PARP-1), and that activated SIRT-1 physically binds with and inhibits PARP-1 activity by a deacetylation dependent mechanism in skeletal muscle from young mice. In contrast, skeletal muscle from aged mice displays higher PARP-1 activity and lower SIRT-1 activity due to decreased intracellular NAD+ content, and as a result reduced muscle performance in response to exercise. Interestingly, injection of PJ34, a PARP-1 inhibitor, in aged mice increased SIRT-1 activity by preserving intracellular NAD+ content, which resulted in higher skeletal muscle mitochondrial biogenesis and performance. We found that the higher activity of PARP-1 in H2O2-treated myotubes or in exercised-skeletal muscles from aged mice is due to an elevated level of PARP-1 acetylation by the histone acetyltransferase General control of amino acid synthesis protein 5-like 2 (GCN-5). These results suggest that activation of SIRT-1 and/or inhibition of PARP-1 may ameliorate skeletal muscle performance in pathophysiological conditions such as sarcopenia and disuse-induced atrophy in aging.

The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high‐ and low‐functioning elderly individuals

Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC-1α, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.

Effects of carnosine on contractile apparatus Ca2+sensitivity and sarcoplasmic reticulum Ca2+release in human skeletal muscle fibers

There is considerable interest in potential ergogenic and therapeutic effects of increasing skeletal muscle carnosine content, although its effects on excitation-contraction (EC) coupling in human muscle have not been defined. Consequently, we sought to characterize what effects carnosine, at levels attained by supplementation, has on human muscle fiber function, using a preparation with all key EC coupling proteins in their in situ positions. Fiber segments, obtained from vastus lateralis muscle of human subjects by needle biopsy, were mechanically skinned, and their Ca(2+) release and contractile apparatus properties were characterized. Ca(2+) sensitivity of the contractile apparatus was significantly increased by 8 and 16 mM carnosine (increase in pCa(50) of 0.073 ± 0.007 and 0.116 ± 0.006 pCa units, respectively, in six type I fibers, and 0.063 ± 0.018 and 0.103 ± 0.013 pCa units, respectively, in five type II fibers). Caffeine-induced force responses were potentiated by 8 mM carnosine in both type I and II fibers, with the potentiation in type II fibers being entirely explicable by the increase in Ca(2+) sensitivity of the contractile apparatus caused by carnosine. However, the potentiation of caffeine-induced responses caused by carnosine in type I fibers was beyond that expected from the associated increase in Ca(2+) sensitivity of the contractile apparatus and suggestive of increased Ca(2+)-induced Ca(2+) release. Thus increasing muscle carnosine content likely confers benefits to muscle performance in both fiber types by increasing the Ca(2+) sensitivity of the contractile apparatus and possibly also by aiding Ca(2+) release in type I fibers, helping to lessen or slow the decline in muscle performance during fatiguing stimulation.

Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large inter-subject variability was observed for all criteria measured. More interestingly, the log (CK(post) /CK(pre)) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r(2) = 0.70 and r = 0.75, r(2) = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans.

MIP/MTMR14 and muscle aging

It is well known that the human aging process is associated with a progressive loss of muscular strength. Characteristic of this decline in muscle performance is the loss of skeletal muscle mass (sarcopenia) that occurs even in the healthy elderly. Indeed, humans can lose as much as 40% of their muscle mass from age 20 to 60. This significant loss of muscle mass and strength has important health and social implications as muscle weakness can contribute to an increased risk of falls and a loss of independence. Therefore, improving our understanding of the mechanisms responsible for sarcopenia and the age-related loss of muscle strength is important. The report by Romero-Suarez et al. [1] provides important new information regarding a potential cellular mechanism that may contribute to sarcopenia. These investigators used a combination of experimental approaches to phenotypically compare wild type old mice with mature mice lacking a novel muscle specific inositide phosphatase (MIP/MTMR14) that plays an important role in muscle calcium homeostasis. Interestingly, the mature MIP/MTMR14 knockout mice displayed phenotypes that closely resembled the muscles of old animals. Indeed, these relatively young knockout mice displayed impaired muscle calcium homeostasis, depressed muscle contractile force production and a loss of muscle mass that is commonly observed in senescent animals. Interestingly, the old wild type mice also displayed impaired muscle calcium homeostasis and decreases in muscle size and contractile function. Importantly, these old mice also possessed reduced muscle levels of MIP/MTMR14. The authors concluded that these findings were consistent with the hypothesis that an age-related loss in MIP/MTMR14 may be a contributory factor to sarcopenia. The findings of Romero-Suarez et al. [1] are exciting and set the stage for future experiments to further examine the molecular role that MIP/MTMR14 plays in the age-related decline in skeletal muscle mass and function. Prior studies by Shen, et al. [2] suggest that MIP/MTMR14 deficiency elevates PtdIns(3,4)P2 and PtdIns(3,5)P2 levels in the sarcoplasmic reticulum. These phosphoinositide derivatives appear to promote calcium leak, contractile dysfunction, and protein catabolism. It remains to be seen whether PtdIns(3,4)P2 and PtdIns(3,5)P2 accumulate in the SR of aged muscles. This is an intriguing possibility. A detailed understanding of the cellular function of MIP/MTMR14 and the molecular events leading to saropenia may lead to clinical countermeasures to slow the age-related loss of muscular strength.

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). OBJECTIVE, DESIGN, AND PATIENTS: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-010-9140-1) contains supplementary material, which is available to authorized users.

Age-related blood flow changes in the rat intrinsic laryngeal muscles

Conclusions. These results indicate that a deceased laryngeal blood flow (BF) could be one contributing factor to age-related phonatory and airway dysfunction. Objective. Studies of non-laryngeal muscles suggest that decreased BF may contribute to an age-related decline in muscle performance. We hypothesized that there is an age-related BF decrease to the intrinsic laryngeal muscles. Materials and methods. Intrinsic laryngeal muscle BF was measured in young (3–6 months old; n=11) and old (28–30 months old; n=21) male Fischer 344 rats during quiet respiration using the radiolabeled microsphere technique. Results. BF to the posterior cricoarytenoid (PCA) was very high even during this submaximal recruitment, consistent with its specialization for oxidative metabolism and fatigue resistance. The results demonstrated significant (p<0.05) age-related BF decreases in the thyroarytenoid (young, 163; old, 64 ml/min/100 g), cricothyroid (young, 104; old, 52 ml/min/100 g), and PCA (young, 404; old, 235 ml/min/100 g).

The response to paired motor cortical stimuli is abolished at a spinal level during human muscle fatigue

During maximal exercise, supraspinal fatigue contributes significantly to the decline in muscle performance but little is known about intracortical inhibition during such contractions. Long-interval inhibition is produced by a conditioning motor cortical stimulus delivered via transcranial magnetic stimulation (TMS) 50-200 ms prior to a second test stimulus. We aimed to delineate changes in this inhibition during a sustained maximal voluntary contraction (MVC). Eight subjects performed a 2 min MVC of elbow flexors. Single test and paired (conditioning-test interval of 100 ms) stimuli were delivered via TMS over the motor cortex every 7-8 s throughout the effort and during intermittent MVCs in the recovery period. To determine the role of spinal mechanisms, the protocol was repeated but the TMS test stimulus was replaced by cervicomedullary stimulation which activates the corticospinal tract. TMS motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were recorded from biceps brachii. Unconditioned MEPs increased progressively with fatigue, whereas CMEPs increased initially but returned to the control value in the final 40 s of contraction. In contrast, both conditioned MEPs and CMEPs decreased rapidly with fatigue and were virtually abolished within 30 s. In recovery, unconditioned responses required <30 s but conditioned MEPs and CMEPs required 90 s to return to control levels. Thus, long-interval inhibition increased markedly as fatigue progressed. Contrary to expectations, subcortically evoked CMEPs were inhibited as much as MEPs. This new phenomenon was also observed in the first dorsal interosseous muscle. Tested with a high intensity conditioning stimulus during a fatiguing maximal effort, long-interval inhibition of MEPs was increased primarily by spinal rather than motor cortical mechanisms. The spinal mechanisms exposed here may contribute to the development of central fatigue in human muscles.

Acute alcohol consumption aggravates the decline in muscle performance following strenuous eccentric exercise

This study investigated the effects of acute moderate alcohol intake on muscular performance during recovery from eccentric exercise-induced muscle damage. Eleven healthy males performed 300 maximal eccentric contractions of the quadriceps muscles of one leg on an isokinetic dynamometer. They then consumed a beverage containing 1 g/kg bodyweight ethanol (as vodka and orange juice) (ALC). On another occasion they performed an equivalent bout of eccentric exercise on the contralateral leg after which they consumed an isocaloric quantity of orange juice (OJ). Measurement of maximal isokinetic (concentric and eccentric) and isometric torque produced across the knee, plasma creatine kinase (CK) concentrations and muscle soreness were made before and at 36 and 60 h following each exercise bout. All measures of muscle performance were significantly reduced at 36 and 60 h post-exercise compared to pre-exercise measures (all p < 0.05). The greatest decreases in peak strength were observed at 36 h with losses of 12%, 28% and 19% occurring for OJ isometric, concentric, and eccentric contractions, respectively. However, peak strength loss was significantly greater in ALC with the same performance measures decreasing by 34%, 40% and 34%, respectively. Post-exercise plasma creatine kinase activity and ratings of muscle soreness were not different between conditions (both p > 0.05). These results indicate that consumption of even moderate amounts of alcohol following eccentric-based exercise magnifies the normally observed losses in dynamic and static strength. Therefore, to minimise exercise related losses in muscle function and expedite recovery, participants in sports involving eccentric muscle work should avoid alcohol-containing beverages in the post-event period.