RESUMO
This study investigated the physiological and gender determinants of the age-related loss of muscle power in 31 healthy middle-aged adults (aged 40-55 years), 28 healthy older adults (70-85 years) and 34 mobility-limited older adults (70-85 years). We hypothesized that leg extensor muscle power would be significantly lower in mobility-limited elders relative to both healthy groups and sought to characterize the physiological mechanisms associated with the reduction of muscle power with aging. Computed tomography was utilized to assess mid-thigh body composition and calculate specific muscle power and strength. Surface electromyography was used to assess rate of neuromuscular activation and muscle biopsies were taken to evaluate single muscle fiber contractile properties. Peak muscle power, strength, muscle cross-sectional area, specific muscle power and rate of neuromuscular activation were significantly lower among mobility-limited elders compared to both healthy groups (P ≤ 0.05). Mobility-limited older participants had greater deposits of intermuscular adipose tissue (P < 0.001). Single fiber contractile properties of type I and type IIA muscle fibers were preserved in mobility-limited elders relative to both healthy groups. Male gender was associated with greater decrements in peak and specific muscle power among mobility-limited participants. Impairments in the rate of neuromuscular activation and concomitant reductions in muscle quality are important physiological mechanisms contributing to muscle power deficits and mobility limitations. The dissociation between age-related changes at the whole muscle and single fiber level suggest that, even among older adults with overt mobility problems, contractile properties of surviving muscle fibers are preserved in an attempt to maintain overall muscle function.
Assuntos
Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Força Muscular/fisiologia , Fatores Etários , Idoso , Estudos Transversais/métodos , Eletromiografia/métodos , Feminino , Humanos , Perna (Membro)/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
OBJECTIVE: The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy. METHODS: We have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full-length human dysferlin from a muscle-specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits. RESULTS: Overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin-null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca(2+)-regulated, dysferlin-binding proteins and endoplasmic reticulum stress chaperone proteins were observed in muscle lysates from transgenic mice as compared with controls. INTERPRETATION: Expression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this.
Assuntos
Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/genética , Doenças Musculares/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Disferlina , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Dosagem de Genes , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença/genética , Humanos , Cifose/genética , Cifose/patologia , Cifose/fisiopatologia , Coxeadura Animal/genética , Coxeadura Animal/patologia , Coxeadura Animal/fisiopatologia , Camundongos , Camundongos Transgênicos , Chaperonas Moleculares/metabolismo , Debilidade Muscular/genética , Debilidade Muscular/patologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Fenótipo , Regiões Promotoras Genéticas/genética , Estresse Fisiológico/genéticaRESUMO
When the contractile properties of single muscle fibres are studied, force is typically normalized by fibre cross-sectional area and expressed as specific force. We studied a set of 2725 chemically skinned human single muscle fibres from 119 healthy adults to determine whether specific force is the optimal way to express the relationship between single-fibre force and size. A linear mixed effects model was used to estimate the slope and slope variability among individuals of log-log plots of force and diameter. For type I fibres, the slope estimate was 0.99 (95% confidence interval 0.36-1.62), and for type IIa fibres it was 0.94 (95% confidence interval 0.77-1.11), indicating that force is proportional to fibre diameter, rather than to cross-sectional area. If force were proportional to cross-sectional area, the slope estimate would be 2.0. In future studies using the chemically skinned single fibre preparation, force may be normalized to fibre diameter rather than cross-sectional area. We propose that a new term, 'normalized force', be used for this variable, with units of newtons per metre. We demonstrate using our data set that when populations of single fibres are compared with one another, the determination of whether the size and force relationship is the same or different is dependent upon the method used to account for fibre size (i.e. specific force versus 'normalized force').
Assuntos
Modelos Biológicos , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Fatores SexuaisRESUMO
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. METHODS: We designed and implemented a multicenter trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n = 185). The primary outcome in both stages was a decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo. RESULTS: Stage 1 selected the 2,700 mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying prespecified sensitivity test, and further supplementary analyses. Prespecified secondary analyses showed no significant differences between CoQ10 at 2,700 mg/day and placebo. There were no safety concerns. INTERPRETATION: CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Antioxidantes/uso terapêutico , Ubiquinona/análogos & derivados , Esclerose Lateral Amiotrófica/mortalidade , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/administração & dosagem , Ubiquinona/efeitos adversos , Ubiquinona/uso terapêuticoRESUMO
Cross-sectional studies are likely to underestimate age-related changes in skeletal muscle strength and mass. The purpose of this longitudinal study was to assess whole muscle and single muscle fiber alterations in the same cohort of 12 older (mean age: start of study 71.1+/-5.4 yr and end of study 80+/-5.3 yr) volunteers (5 men) evaluated 8.9 yr apart. No significant changes were noted at follow-up in body weight, body mass index, and physical activity. Muscle strength, evaluated using isokinetic dynamometry, and whole muscle specific force of the knee extensors were significantly lower at follow-up. This was accompanied by a significant reduction (5.7%) in cross-sectional area of the total anterior muscle compartment of the thigh as evaluated by computed tomography. Muscle histochemistry showed no significant changes in fiber type distribution or fiber area. Experiments with chemically skinned single muscle fibers (n=411) demonstrated no change in type I fiber size but an increase in IIA fiber diameter. A trend toward an increase in maximal force in both fiber types was observed. Maximum unloaded shortening velocity did not change. In conclusion, single muscle fiber contractile function may be preserved in older humans in the presence of significant alterations at the whole muscle level. This suggests that surviving fibers compensate to partially correct muscle size deficits in an attempt to maintain optimal force-generating capacity.
Assuntos
Envelhecimento/fisiologia , Fibras Musculares Esqueléticas/ultraestrutura , Tecido Adiposo/fisiologia , Idoso , Tamanho Celular , Feminino , Histocitoquímica , Humanos , Estudos Longitudinais , Masculino , Fibras Musculares Esqueléticas/fisiologia , Relaxamento Muscular/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/crescimento & desenvolvimento , Cadeias Pesadas de Miosina/metabolismo , Coxa da Perna/anatomia & histologia , Tomografia Computadorizada por Raios XRESUMO
Amyotrophic lateral sclerosis (ALS) is a devastating, progressive motor neuron disorder that poses a myriad of clinical problems. Patients who have ALS are best cared for in a multidisciplinary fashion, with involvement of clinicians from various specialties, including neurology, physical medicine and rehabilitation, pulmonary medicine, clinical nurse specialists or nurse practitioners, physical and occupational therapists, speech language pathologists, dietitians, psychologists, social workers, and case managers. This article provides a summary of the current research into the rehabilitation of ALS, including the role of exercise, spasticity management, mood disorders, pain, and palliative care.
Assuntos
Esclerose Lateral Amiotrófica/terapia , Assistência Integral à Saúde/organização & administração , Planejamento de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Progressão da Doença , Humanos , Assistência Terminal/organização & administraçãoRESUMO
The current investigation was designed to: (a) assess the impact of aging on elastic characteristics of single skeletal muscle fibers from young (N = 6) and older men (N = 6); and (b) correlate the potential changes, with the fiber contractile properties. Chemically skinned single muscle fibers (n = 235) from vastus lateralis muscle were maximally activated. Maximal force and cross-sectional area were measured, and specific force calculated. The slack test was used to measure maximal unloaded shortening velocity. A quick release of 0.15% of fiber length was applied to determine instantaneous stiffness. The myosin heavy chain isoform composition of each single fiber was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aging induces changes in both fiber elasticity (i.e., increased instantaneous stiffness) and contractility (i.e., reduced specific force and unloaded shortening velocity) in type I and IIa fibers. However, the changes in fiber stiffness may not directly influence contractile characteristics alterations.
Assuntos
Envelhecimento/fisiologia , Contração Muscular , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Adulto , Idoso , Elasticidade , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Isoformas de Proteínas/metabolismoRESUMO
In this article, non-neurologic causes of neck and back pain are reviewed. Musculoskeletal pain generators include muscle, tendon, ligament, intervertebral disc, articular cartilage, and bone. Disorders that can produce neck and back pain include muscle strain, ligament sprain, myofascial pain, fibromyalgia, facet joint pain, internal disc disruption, somatic dysfunction, spinal fracture, vertebral osteomyelitis, and polymyalgia rheumatica. Atlantoaxial instability and atlanto-occipital joint pain are additional causes of neck pain. Back pain resulting from vertebral compression fracture, Scheuermann's disease, spondylolysis and spondylolisthesis, pregnancy, Baastrup's disease, sacroiliac joint dysfunction, and sacral stress fracture is discussed.
Assuntos
Dor nas Costas/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Cervicalgia/fisiopatologia , Dor nas Costas/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Doenças Musculoesqueléticas/diagnóstico , Cervicalgia/diagnóstico , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Hereditary metabolic disorders can cause rhabdomyolysis in athletes. Team physicians should be aware of the presentation, workup, and management of the most common of these disorders, carnitine palmitoyltransferase (CPT) II deficiency and muscle phosphorylase deficiency. METHODS: The case of a collegiate athlete with recurrent bouts of rhabdomyolysis is presented, and the diagnostic workup is discussed. RESULTS: The patient described in this case has CPT II deficiency. The diagnosis and management of CPT II deficiency and muscle phosphorylase deficiency (McArdle's disease) are discussed. CONCLUSION: Athletes with rhabdomyolysis, in the absence of an obvious cause such as drug toxicity, severe trauma, or excessive exercise, should be evaluated for the presence of a metabolic myopathy.
Assuntos
Rabdomiólise , Esportes , Adulto , Carnitina O-Palmitoiltransferase/deficiência , Feminino , Doença de Depósito de Glicogênio Tipo V/terapia , Humanos , Massachusetts , Rabdomiólise/diagnóstico , Rabdomiólise/metabolismo , Rabdomiólise/fisiopatologia , Rabdomiólise/terapiaRESUMO
PURPOSE: This study was conducted to determine whether differences in power at the single muscle fiber level contribute to sex differences in whole muscle power production in the elderly. METHODS: A total of 16 sedentary older persons (10 women, 6 men), mean age 72 yr, had percutaneous needle biopsy of musculus vastus lateralis. Chemically skinned single muscle fibers were activated with Ca for maximal isometric force measurement (Po). The slack test was performed to determine maximal unloaded shortening velocity (Vo). Force-velocity and power curves were generated via a series of isotonic contractions, allowing measurement of peak power and specific power. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to determine myosin heavy chain composition of single muscle fibers. Whole muscle strength, velocity, and power were measured for knee extension and double leg press. RESULTS: Men had greater whole muscle strength, power, and velocity compared with women. Studied were 274 type I and 33 type IIa single fibers. No significant sex differences were found for fiber size, Po, specific force, Vo, power, or specific power in type I or IIa fibers. CONCLUSIONS: Single muscle fiber quality in older women is equivalent to that in older men and can not explain the differences seen in whole muscle strength, power, or function.
Assuntos
Fibras Musculares Esqueléticas/fisiologia , Fatores Sexuais , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Humanos , Contração Isométrica , Contração Isotônica , Masculino , Músculo Esquelético/fisiologiaRESUMO
Five patients with untreated dermatomyositis, five with inclusion body myositis, and 16 healthy elderly volunteer subjects (controls) underwent open (dermatomyositis and inclusion body myositis) or percutaneous (controls) muscle biopsy. Biopsied muscles included deltoid, biceps and vastus lateralis. Chemically skinned single muscle fibers were activated with Ca(+2); the slack test was performed to determine maximal unloaded shortening velocity (Vo). Parameters measured include single fiber cross sectional area, maximal force, specific force and Vo. 429 Type I and 94 Type IIA fibers were studied. Cross sectional area and maximal force were greater in inclusion body myositis than dermatomyositis or control for Type I and IIA fibers. Specific force of Type I fibers was similar in inclusion body myositis and dermatomyositis but greater than in controls. Vo was greater in Type I, but not IIA, fibers in dermatomyositis compared with inclusion body myositis and controls. The force and velocity generating capacity of single muscle fibers is preserved in patients with dermatomyositis and inclusion body myositis suggesting that dysfunction of the contractile proteins does not contribute to clinical muscle weakness.
Assuntos
Dermatomiosite/fisiopatologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiopatologia , Miosite de Corpos de Inclusão/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Dermatomiosite/patologia , Feminino , Humanos , Técnicas In Vitro , Contração Isométrica/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/classificação , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/patologia , Tamanho do Órgão , Resistência Física , Valores de ReferênciaRESUMO
In the 60 years since Lou Gehrig died from amyotrophic lateral sclerosis (ALS) there have been numerous advances in our understanding of this disease. However, scant progress has been made regarding disease-altering treatments. Today most physicians still recommend vitamin E, which is the treatment Gehrig himself received. In this paper we will review what is currently known about the pathophysiology of ALS as well as the history of clinical trials in ALS. We indicate current and future directions in research and clinical trials, and also argue that a logical next step for clinical trials in ALS should be combination drug treatment.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Esclerose Lateral Amiotrófica/enzimologia , Esclerose Lateral Amiotrófica/etiologia , Animais , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Creatina/uso terapêutico , Humanos , Riluzol/uso terapêutico , Resultado do TratamentoRESUMO
The anterior horn cell diseases, with the exception of polio, are progressive degenerative diseases of the motor neurons. These disorders include SMA types I to III in children and familial and sporadic ALS and its variants (PMA, PLS, and PBP), Kennedy's disease, and SMA type IV in adults. The electrodiagnostic study is a crucial step in the diagnostic process for all of these disorders. In general, motor NCS may be normal or reveal low CMAP amplitudes with relatively normal conduction velocities. Sensory NCS, except in the case of Kennedy's disease, are normal. The NEE is notable for the often abundant presence of abnormal spontaneous activity, including fibrillation potentials and positive sharp waves, fasciculation potentials, and complex repetitive discharges. Motor unit morphology is abnormal, with polyphasic motor units and large amplitude and duration MUAPs when the disease is slowly progressive. Recruitment in affected muscles is reduced with abnormally rapidly firing motor units. To diagnose a widespread disorder of the motor neurons, abnormalities must be present in multiple muscles with different nerve root and peripheral nerve innervation in multiple limbs. The Lambert Criteria and the El Escorial Criteria are the two most widely accepted sets of electrodiagnostic criteria for ALS. The electrodiagnostic diagnosis must be supported by appropriate history and physical examination findings and the exclusion, via neuroimaging and laboratory testing, of other diseases that may mimic a generalized disorder of the motor neurons.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Eletrodiagnóstico/métodos , Doença dos Neurônios Motores/diagnóstico , Diagnóstico Diferencial , Diagnóstico por Imagem , Humanos , Atrofia Muscular Espinal/diagnóstico , Poliomielite/diagnósticoAssuntos
Eletromiografia/métodos , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiopatologia , Doenças Neuromusculares/fisiopatologia , Animais , Biópsia por Agulha/métodos , Humanos , Contração Isométrica/fisiologia , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismoRESUMO
Myostatin inhibitors are being investigated as treatments for myopathies. We assessed single muscle fiber contractile properties before and after 6 months of study drug in 6 patients with facioscapulohumeral, Becker, and limb-girdle muscular dystrophy. Five of the patients received MYO-029, a myostatin inhibitor, and 1 received placebo. The chemically skinned single muscle fiber preparation was used to measure single fiber force, specific force, maximum unloaded shortening velocity, power, and specific power in type I and IIa fibers from each subject. In 4 of 5 patients who received MYO-029, improvement was seen in single muscle fiber contractile properties; thus, there may be a beneficial effect of myostatin inhibition on muscle physiology at the cellular level. No improvement was seen in the patient who received placebo. This finding may be clinically relevant in spite of the fact that quantitative muscle strength measurements in our patients did not improve. Further studies of myostatin inhibition as a treatment for muscular dystrophy are warranted, and single muscle fiber contractile studies are a useful assay for muscle function at the cellular level.
Assuntos
Anticorpos/administração & dosagem , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Distrofias Musculares/tratamento farmacológico , Miostatina/antagonistas & inibidores , Adulto , Anticorpos/efeitos adversos , Bioensaio/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Distrofias Musculares/metabolismo , Distrofias Musculares/fisiopatologia , Miostatina/metabolismo , Placebos , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
A 46-year-old man with a 1-year history of distal paresthesias and mild distal weakness subacutely developed paralysis of the left hand. Electrodiagnostic evaluation revealed a demyelinating peripheral neuropathy that met criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Magnetic resonance imaging of the brain revealed a mass that enhanced with contrast, but revealed focal myelin loss with intense macrophage activity and axonal preservation on biopsy. The mass and hand weakness improved following steroid therapy. The combination of CIDP and central demyelination with mass effect broadens the spectrum of demyelinating disease in association with CIDP.
Assuntos
Encefalopatias/complicações , Encefalopatias/diagnóstico , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Potenciais de Ação , Axônios/química , Axônios/patologia , Axônios/ultraestrutura , Encefalopatias/patologia , Doenças Desmielinizantes/patologia , Eletrodiagnóstico , Força da Mão , Humanos , Imuno-Histoquímica , Macrófagos/química , Macrófagos/patologia , Macrófagos/ultraestrutura , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Debilidade Muscular/diagnóstico , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/fisiopatologia , Bainha de Mielina , Condução Nervosa , Proteínas de Neurofilamentos/análise , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Esteroides/uso terapêuticoRESUMO
Spinal cord injury (SCI) results in muscle weakness but the degree of impairment at the level of single fibers is not known. The purpose of this study was to examine the effects of T9-level SCI on single muscle fibers from the tibialis anterior of rats. Significant decreases in cross-sectional area (CSA), maximal force (Po), and specific force (SF = Po/CSA) were noted at 2 weeks. Atrophy and force-generating capacity were reversed at 4 weeks, but SF remained impaired. Maximum shortening velocity (Vo) did not change after injury. SCI thus appears to affect various contractile properties of single muscle fibers differently. Normal cage activity may partially restore function but new interventions are needed to restore muscle fiber quality.
Assuntos
Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Análise de Variância , Animais , Comportamento Animal , Western Blotting/métodos , Modelos Animais de Doenças , Masculino , Cadeias Pesadas de Miosina/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The origins of the smaller age-related decrease in eccentric force compared to isometric and concentric conditions in vivo remain unclear. Could this originate from contractile elements of muscle cells? The main intent of the current investigation was to assess the force behavior of muscle cells with aging, during lengthening. Chemically skinned single muscle fibers (n=235) from m. vastus lateralis of six young (mean age 31.6 years) and six older men (mean age 66.1 years) were maximally activated with pCa 4.5 at 15 degrees C. Maximal isometric force and cross-sectional area were measured allowing the calculation of the tension (T (0)). A quick stretch (2 nm per half-sarcomere length) was applied and caused an immediate increase in tension followed by a decrease and a secondary delayed and transient rise in tension (phase 3); finally, the tension recovered a steady state value (phase 4). The tension enhancements during phase 3 (DeltaT (3)) and phase 4 (DeltaT (4)) were evaluated. The myosin heavy-chain isoform composition of each single fiber was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. DeltaT (3) and DeltaT (4) were preserved in older men for both type I and IIa fibers despite a reduction in T (0). Therefore, the age-related preservation of the tension increments after a quick stretch in single muscle fibers could explain in part the smaller decrease in force during eccentric contractions compared to isometric and concentric conditions in vivo with aging usually observed.
Assuntos
Envelhecimento/fisiologia , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Estimulação Física/métodos , Adulto , Fatores Etários , Idoso , Células Cultivadas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estresse MecânicoRESUMO
In the past, patients with neuromuscular diseases were advised not to exercise because of the fear that too much exercise might produce "overuse weakness." No controlled studies have demonstrated that the phenomenon of overuse weakness actually exists. Most studies of exercise training in patients with neuromuscular disease, despite methodologic limitations, suggest that strength and aerobic capacity gains can occur in patients with slowly progressive disorders. Four forms of exercise training are relevant to patients with neuromuscular disorders: flexibility, strengthening, aerobic, and balance exercises. The literature regarding these forms of exercise in patients with neuromuscular disorders is summarized in this article, and recommendations are made regarding the direction future research on exercise in this population should take.