RESUMO
BACKGROUND: Older adults exhibit a slower recovery of muscle mass following disuse atrophy than young adults. At a smaller scale, muscle fibre cross-sectional area (i.e., sarcomeres in parallel) exhibits this same pattern. Less is known, however, about age-related differences in the recovery of muscle fibre length, driven by increases in serial sarcomere number (SSN), following disuse. The purpose of this study was to investigate age-related differences in SSN adaptations and muscle mechanical function during and following muscle immobilization. We hypothesized that older adult rats would experience a similar magnitude of SSN loss during immobilization, however, take longer to recover SSN than young following cast removal, which would limit the recovery of muscle mechanical function. METHODS: We casted the plantar flexors of young (8 months) and old (32 months) male rats in a shortened position for 2 weeks, and assessed recovery during 4 weeks of voluntary ambulation. Following sacrifice, legs were fixed in formalin for measurement of soleus SSN and physiological cross-sectional area (PCSA) with the un-casted soleus acting as a control. Ultrasonographic measurements of pennation angle (PA) and muscle thickness (MT) were conducted weekly. In-vivo active and passive torque-angle relationships were constructed pre-cast, post-cast, and following 4 weeks of recovery. RESULTS: From pre- to post-cast, young and older adult rats experienced similar decreases in SSN (-20%, P < 0.001), muscle wet weight (-25%, P < 0.001), MT (-30%), PA (-15%, P < 0.001), and maximum isometric torque (-40%, P < 0.001), but there was a greater increase in passive torque in older (+ 180%, P < 0.001) compared to young adult rats (+ 68%, P = 0.006). Following cast removal, young exhibited quicker recovery of SSN and MT than old, but SSN recovered sooner than PA and MT in both young and old. PCSA nearly recovered and active torque fully recovered in young adult rats, whereas in older adult rats these remained unrecovered at â¼ 75%. CONCLUSIONS: This study showed that older adult rats retain a better ability to recover longitudinal compared to parallel muscle morphology following cast removal, making SSN a highly adaptable target for improving muscle function in elderly populations early on during rehabilitation.
Assuntos
Envelhecimento , Músculo Esquelético , Sarcômeros , Animais , Masculino , Sarcômeros/metabolismo , Sarcômeros/patologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/diagnóstico por imagem , Ratos , Ratos Endogâmicos F344 , Transtornos Musculares Atróficos/fisiopatologia , Transtornos Musculares Atróficos/patologia , Transtornos Musculares Atróficos/diagnóstico por imagem , Transtornos Musculares Atróficos/etiologia , Recuperação de Função Fisiológica , Elevação dos Membros Posteriores/efeitos adversos , Adaptação FisiológicaRESUMO
Periods of skeletal muscle disuse lead to rapid declines in muscle mass (atrophy), which is fundamentally underpinned by an imbalance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). The complex interplay of molecular mechanisms contributing to the altered regulation of muscle protein balance during disuse have been investigated but rarely synthesised in the context of humans. This narrative review discusses human models of muscle disuse and the ensuing inversely exponential rate of muscle atrophy. The molecular processes contributing to altered protein balance are explored, with a particular focus on growth and breakdown signalling pathways, mitochondrial adaptations and neuromuscular dysfunction. Finally, key research gaps within the disuse atrophy literature are highlighted providing future avenues to enhance our mechanistic understanding of human disuse atrophy.
Assuntos
Proteínas Musculares , Músculo Esquelético , Atrofia Muscular , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteínas Musculares/metabolismo , Transdução de Sinais , Imobilização/efeitos adversos , Transtornos Musculares Atróficos/metabolismo , Transtornos Musculares Atróficos/patologia , Transtornos Musculares Atróficos/fisiopatologiaRESUMO
Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis-induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days. Soleus (SOL) and extensor digitorum longus (EDL) were dissected for in vitro muscle mechanics, morphological, and histological assessments. In SOL muscles, both CLP+NA and SHAM+HLS conditions elicited ~20% reduction in specific force (p < 0.05). When combined, CLP+HLS elicited ~35% decrease in specific force (p < 0.05). Loss of maximal specific force (~8%) was evident in EDL muscles only in CLP+HLS mice (p < 0.05). CLP+HLS reduced muscle fiber cross-sectional area (CSA) and mass in SOL (p < 0.05). In EDL muscles, CLP+HLS decreased absolute mass to a smaller extent (p < 0.05) with no changes in CSA. Immunohistochemistry revealed substantial myeloid cell infiltration (CD68+) in SOL, but not in EDL muscles, of CLP+HLS mice (p < 0.05). Combining CLP with HLS is a feasible model to study sepsis-induced myopathy in mice. Hindlimb disuse combined with sepsis induced muscle dysfunction and immune cell infiltration in a muscle dependent manner. These findings highlight the importance of rehabilitative interventions in septic hosts to prevent muscle disuse and help attenuate the myopathy.
Assuntos
Elevação dos Membros Posteriores/efeitos adversos , Músculo Esquelético/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Sepse/fisiopatologia , Animais , Membro Posterior/patologia , Elevação dos Membros Posteriores/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Doenças Musculares/etiologia , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/patologia , Sepse/complicações , Sepse/patologiaRESUMO
Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.
Assuntos
Angiotensina I/administração & dosagem , Diafragma/efeitos dos fármacos , Debilidade Muscular/prevenção & controle , Transtornos Musculares Atróficos/prevenção & controle , Fragmentos de Peptídeos/administração & dosagem , Respiração Artificial/efeitos adversos , Animais , Diafragma/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Infusões Intravenosas , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
A large set of FoxOs-dependent genes play a primary role in controlling muscle mass during hindlimb unloading. Mitochondrial dysfunction can modulate such a process. We hypothesized that endurance exercise before disuse can protect against disuse-induced muscle atrophy by enhancing peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) expression and preventing mitochondrial dysfunction and energy-sensing AMP-activated protein kinase (AMPK) activation. We studied cross sectional area (CSA) of muscle fibers of gastrocnemius muscle by histochemistry following 1, 3, 7, and 14 days of hindlimb unloading (HU). We used Western blotting and qRT-PCR to study mitochondrial dynamics and FoxOs-dependent atrogenes' expression at 1 and 3 days after HU. Preconditioned animals were submitted to moderate treadmill exercise for 7 days before disuse. Exercise preconditioning protected the gastrocnemius from disuse atrophy until 7 days of HU. It blunted alterations in mitochondrial dynamics up to 3 days after HU and the expression of most atrogenes at 1 day after disuse. In preconditioned mice, the activation of atrogenes resumed 3 days after HU when mitochondrial dynamics, assessed by profusion and pro-fission markers (mitofusin 1, MFN1, mitofusin 2, MFN2, optic atrophy 1, OPA1, dynamin related protein 1, DRP1 and fission 1, FIS1), PGC1α levels, and AMPK activation were at a basal level. Therefore, the normalization of mitochondrial dynamics and function was not sufficient to prevent atrogenes activation just a few days after HU. The time course of sirtuin 1 (SIRT1) expression and content paralleled the time course of atrogenes' expression. In conclusion, seven days of endurance exercise counteracted alterations of mitochondrial dynamics and the activation of atrogenes early into disuse. Despite the normalization of mitochondrial dynamics, the effect on atrogenes' suppression died away within 3 days of HU. Interestingly, muscle protection lasted until 7 days of HU. A longer or more intense exercise preconditioning may prolong atrogenes suppression and muscle protection.
Assuntos
Elevação dos Membros Posteriores/fisiologia , Membro Posterior/fisiopatologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Biomarcadores/metabolismo , Membro Posterior/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Transtornos Musculares Atróficos/metabolismo , Transtornos Musculares Atróficos/fisiopatologiaRESUMO
Objective: In addition to the split hand sign, other split phenomena of different muscles also exist in amyotrophic lateral sclerosis (ALS). We analyzed the incidence of split phenomena in multiple antagonistic muscle groups in ALS patients and explored whether clinical factors affected their occurrence.Methods: 618 ALS patients were included from a single ALS center. Muscle strength in upper and lower limbs was evaluated using the modified Medical Research Council (MRC) scoring system (range from 1 to 13). Split phenomena between different antagonistic muscle groups were summarized, and the correlations with clinical factors were analyzed.Results: Split phenomena were detected in 22.3% antagonistic muscles for flexion and extension of the elbow, 11.9% for the wrist, 23.9% for fingers, 18.2% for the ankle, and 14.7% for toes. These manifestations were characterized by preferential wasting of the elbow, wrist, and finger extensor muscles compared with the flexor muscles, and the ankle and toe dorsiflexor muscles compared with the plantar flexor muscles. The presence of muscle wasting was more common when the muscle strength was stronger than a modified MRC grade 6. No definite correlation was found between split phenomena and clinical factors, including age-at-onset, gender, disease duration, the region of onset, and pyramidal tract damage.Discussion: Split phenomena of antagonistic muscle groups widely exist in ALS patients. No definitive and consistent clinical factors were observed that affected the occurrence of these phenomena.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/fisiopatologia , Força Muscular , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Adulto , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Atrofia Muscular/etiologia , Transtornos Musculares Atróficos/etiologia , Extremidade Superior/fisiopatologiaRESUMO
BACKGROUND/AIM: To assess the prognostic effect of muscle loss after esophagectomy and before discharge. PATIENTS AND METHODS: This study retrospectively analysed 159 consecutive patients with oesophageal and gastroesophageal junction cancer who underwent esophagectomy between August 2011 and October 2015. Body composition was evaluated one week before surgery and at discharge using a bioelectrical impedance analyser. RESULTS: The median rate of muscle mass loss (RMML) was 4.38% (range=-3.3 to +18.8). Patients with increased RMML had significantly poorer outcomes of overall survival than those with decreased RMML (p=0.015). On multivariate analysis, RMML [≥4.38, hazard ratio (HR)=2.033, 95% confidence interval (CI)=1.018-5.924, p=0.044) and pathological tumour depth (≥2, HR=3.099, 95%CI=1.339-7.172, p=0.008) were selected as independent prognostic factors. CONCLUSION: RMML after esophagectomy is indicative of poor prognosis in patients with esophageal cancer.
Assuntos
Neoplasias Esofágicas/fisiopatologia , Esofagectomia/métodos , Junção Esofagogástrica/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Neoplasias Gástricas/fisiopatologia , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transtornos Musculares Atróficos/etiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
FHL1-related myopathies, including reducing body myopathy (RBM), X-linked scapulo-axio-peroneal myopathy, rigid spine syndrome, X-linked myopathy with postural muscle atrophy (XMPMA), X-linked Emery-Dreifuss muscular dystrophy and hypertrophic cardiomyopathy, are clinically and pathologically heterogeneous disorders caused by FHL1 gene mutations. According to previous reports, the first three types are myopathies with reducing bodies observed in biopsies, and the last three are myopathies without reducing bodies. We report four FHL1-related myopathy patients, including an XMPMA patient and a RBM family with three patients. Clinical information, muscle biopsies, electromyograms and genetic testing were obtained. Muscle weakness and atrophy, spinal rigidity, and joint contracture were present in the RBM family. The XMPMA patient showed a pseudoathletic appearance with muscle weakness and atrophy, spinal rigidity and deformity. The index patient of the RBM family underwent two muscle biopsies to find reducing bodies. Interestingly, these muscle biopsies revealed reducing bodies and rimmed vacuoles not only in the RBM family but also in the XMPMA patient. Next-generation sequencing identified a reported single missense mutation c.448 C>T (p. C150R) in the RBM family and a novel mutation c.814T>C (p. S272P) in the XMPMA patient. Therefore, FHL1-related myopathies overlap substantially and may not be simply classified into subtypes depending on reducing bodies. Biopsies of additional affected muscles can aid in finding reducing bodies. We report the first XMPMA patient with a novel FHL1 mutation and reducing bodies in a muscle biopsy in China.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas com Domínio LIM/genética , Proteínas Musculares/genética , Músculo Esquelético/patologia , Transtornos Musculares Atróficos/genética , Transtornos Musculares Atróficos/patologia , Adulto , China , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Linhagem , Adulto JovemRESUMO
BACKGROUND: Disuse atrophy from immobilization is the result of decreased neural activity and muscle unloading. METHODS: We studied the impact of disuse on hand intrinsic compound muscle action potentials (CMAPs) in a cohort of 39 patients with unilateral 6-week immobilization of the hand in a cast, after distal radius fracture. We excluded patients with nerve injury. We compared side-to-side CMAP characteristics at the time of cast removal and at a subsequent follow-up visit, after a mean interval of 7.8 weeks. RESULTS: Statistically significant reductions in CMAP amplitude were noted for the abductor pollicis brevis (29.2%), abductor digiti minimi (19.0%), and first dorsal interosseus (24.9%). There was partial repair of the relative CMAP reduction at the follow-up visit (20.1%, 10.7%, and 8.7%, respectively). There was no significant change in CMAP duration. CONCLUSIONS: These results provide a framework for quantifying the degree of hand intrinsic CMAP amplitude reduction attributed to disuse.
Assuntos
Potenciais de Ação , Músculo Esquelético/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moldes Cirúrgicos , Eletromiografia , Feminino , Mãos , Humanos , Imobilização , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/terapia , Sensação , Adulto JovemRESUMO
Massive tears of the rotator cuff (RC) are associated with chronic muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. The microenvironment of diseased muscle often impairs efficient engraftment and regenerative activity of transplanted myogenic precursors. Accumulating myofibroblasts and fat cells disrupt the muscle stem cell niche and myogenic cell signaling and deposit excess disorganized connective tissue. Therefore, restoration of the damaged stromal niche with non-fibro-adipogenic cells is a prerequisite to successful repair of an injured RC. We generated from human embryonic stem cells (hES) a potentially novel subset of PDGFR-ß+CD146+CD34-CD56- pericytes that lack expression of the fibro-adipogenic cell marker PDGFR-α. Accordingly, the PDGFR-ß+PDGFR-α- phenotype typified non-fibro-adipogenic, non-myogenic, pericyte-like derivatives that maintained non-fibro-adipogenic properties when transplanted into chronically injured murine RCs. Although administered hES pericytes inhibited developing fibrosis at early and late stages of progressive muscle degeneration, transplanted PDGFR-ß+PDGFR-α+ human muscle-derived fibro-adipogenic progenitors contributed to adipogenesis and greater fibrosis. Additionally, transplanted hES pericytes substantially attenuated muscle atrophy at all tested injection time points after injury. Coinciding with this observation, conditioned medium from cultured hES pericytes rescued atrophic myotubes in vitro. These findings imply that non-fibro-adipogenic hES pericytes recapitulate the myogenic stromal niche and may be used to improve cell-based treatments for chronic muscle disorders.
Assuntos
Células-Tronco Embrionárias Humanas/fisiologia , Transtornos Musculares Atróficos/terapia , Pericitos/transplante , Lesões do Manguito Rotador/complicações , Manguito Rotador/patologia , Animais , Diferenciação Celular , Linhagem Celular , Doença Crônica/terapia , Modelos Animais de Doenças , Feminino , Fibrose , Humanos , Injeções Intralesionais , Camundongos , Desenvolvimento Muscular/fisiologia , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/patologia , Transtornos Musculares Atróficos/fisiopatologia , Pericitos/fisiologia , Manguito Rotador/fisiopatologia , Transplante Heterólogo/métodosRESUMO
Skeletal muscle atrophy is a clinically important outcome of disuse because of injury, immobilization, or bed rest. Disuse atrophy is accompanied by mitochondrial dysfunction, which likely contributes to activation of the muscle atrophy program. However, the linkage of muscle mass and mitochondrial energetics during disuse atrophy and its recovery is incompletely understood. Transcriptomic analysis of muscle biopsies from healthy older adults subject to complete bed rest revealed marked inhibition of mitochondrial energy metabolic pathways. To determine the temporal sequence of muscle atrophy and changes in intramyocellular lipid and mitochondrial energetics, we conducted a time course of hind limb unloading-induced atrophy in adult mice. Mitochondrial respiration and calcium retention capacity were diminished, whereas H2O2 emission was increased within 3 days of unloading before significant muscle atrophy. These changes were associated with a decrease in total cardiolipin and profound changes in remodeled cardiolipin species. Hind limb unloading performed in muscle-specific peroxisome proliferator-activated receptor-γ coactivator-1α/ß knockout mice, a model of mitochondrial dysfunction, did not affect muscle atrophy but impacted muscle function. These data suggest early mitochondrial remodeling affects muscle function but not mass during disuse atrophy. Early alterations in mitochondrial energetics and lipid remodeling may represent novel targets to prevent muscle functional impairment caused by disuse and to enhance recovery from periods of muscle atrophy.
Assuntos
Metabolismo Energético , Mitocôndrias Musculares/metabolismo , Transtornos Musculares Atróficos/metabolismo , Idoso , Animais , Repouso em Cama , Cálcio/metabolismo , Cardiolipinas/metabolismo , Feminino , Elevação dos Membros Posteriores , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Transtornos Musculares Atróficos/fisiopatologia , Consumo de Oxigênio , Recuperação de Função Fisiológica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
Electrical stimulation (ES)-induced muscle contraction has multiple effects; however, mechano-responsiveness of bone tissue declines with age. Here, we investigated whether daily low-frequency ES-induced muscle contraction treatment reduces muscle and bone loss and ameliorates bone fragility in early-stage disuse musculoskeletal atrophy in aged rats. Twenty-seven-month-old male rats were assigned to age-matched groups comprising the control (CON), sciatic nerve denervation (DN), or DN with direct low-frequency ES (DN+ES) groups. The structural and mechanical properties of the trabecular and cortical bone of the tibiae, and the morphological and functional properties of the tibialis anterior (TA) muscles were assessed one week after DN. ES-induced muscle contraction force mitigated denervation-induced muscle and trabecular bone loss and deterioration of the mechanical properties of the tibia mid-diaphysis, such as the stiffness, but not the maximal load, in aged rats. The TA muscle in the DN+ES group showed significant improvement in the myofiber cross-sectional area and muscle force relative to the DN group. These results suggest that low-frequency ES-induced muscle contraction treatment retards trabecular bone and muscle loss in aged rats in early-stage disuse musculoskeletal atrophy, and has beneficial effects on the functional properties of denervated skeletal muscle.
Assuntos
Envelhecimento/fisiologia , Terapia por Estimulação Elétrica/métodos , Músculo Esquelético/fisiopatologia , Transtornos Musculares Atróficos/terapia , Osteoporose/terapia , Animais , Densidade Óssea/fisiologia , Modelos Animais de Doenças , Masculino , Contração Muscular/fisiologia , Denervação Muscular/efeitos adversos , Músculo Esquelético/inervação , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/fisiopatologia , Osteoporose/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Tíbia/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Successful strategies to halt or reverse sarcopenia require a basic understanding of the factors that cause muscle loss with age. Acute periods of muscle loss in older individuals have an incomplete recovery of muscle mass and strength, thus accelerating sarcopenic progression. The purpose of the current study was to further understand the mechanisms underlying the failure of old animals to completely recover muscle mass and function after a period of hindlimb unloading. METHODS: Hindlimb unloading was used to induce muscle atrophy in Fischer 344-Brown Norway (F344BN F1) rats at 24, 28, and 30 months of age. Rats were hindlimb unloaded for 14 days and then reloaded at 24 months (Reloaded 24), 28 months (Reloaded 28), and 24 and 28 months (Reloaded 24/28) of age. Isometric torque was determined at 24 months of age (24 months), at 28 months of age (28 months), immediately after 14 days of reloading, and at 30 months of age (30 months). During control or reloaded conditions, rats were labelled with deuterium oxide (D2 O) to determine rates of muscle protein synthesis and RNA synthesis. RESULTS: After 14 days of reloading, in vivo isometric torque returned to baseline in Reloaded 24, but not Reloaded 28 and Reloaded 24/28. Despite the failure of Reloaded 28 and Reloaded 24/28 to regain peak force, all groups were equally depressed in peak force generation at 30 months. Increased age did not decrease muscle protein synthesis rates, and in fact, increased resting rates of protein synthesis were measured in the myofibrillar fraction (Fractional synthesis rate (FSR): %/day) of the plantaris (24 months: 2.53 ± 0.17; 30 months: 3.29 ± 0.17), and in the myofibrillar (24 months: 2.29 ± 0.07; 30 months: 3.34 ± 0.11), collagen (24 months: 1.11 ± 0.07; 30 months: 1.55 ± 0.14), and mitochondrial (24 months: 2.38 ± 0.16; 30 months: 3.20 ± 0.10) fractions of the tibialis anterior (TA). All muscles increased myofibrillar protein synthesis (%/day) in Reloaded 24 (soleus: 3.36 ± 0.11, 5.23 ± 0.19; plantaris: 2.53 ± 0.17, 3.66 ± 0.07; TA: 2.29 ± 0.14, 3.15 ± 0.12); however, in Reloaded 28, only the soleus had myofibrillar protein synthesis rates (%/day) >28 months (28 months: 3.80 ± 0.10; Reloaded 28: 4.86 ± 0.19). Across the muscles, rates of protein synthesis were correlated with RNA synthesis (all muscles combined, R2 = 0.807, P < 0.0001). CONCLUSIONS: These data add to the growing body of literature that indicate that changes with age, including following disuse atrophy, differ by muscle. In addition, our findings lead to additional questions of the underlying mechanisms by which some muscles are maintained with age while others are not.
Assuntos
Envelhecimento/patologia , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Transtornos Musculares Atróficos/fisiopatologia , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Modelos Animais de Doenças , Elevação dos Membros Posteriores/efeitos adversos , Masculino , Fibras Musculares Esqueléticas/fisiologia , Proteínas Musculares/metabolismo , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/genética , Transtornos Musculares Atróficos/metabolismo , Tamanho do Órgão , Biossíntese de Proteínas , Ratos , Ratos Endogâmicos F344 , TorqueRESUMO
Disuse situations can have serious adverse health consequences in the elderly, including mainly functional impairment with subsequent increase in the risk of falls or morbimortality. The present review provides clinicians and care givers with detailed and practical information on the feasibility and effectiveness of physical strategies that are currently available to prevent or attenuate the functional decline that occurs secondarily to disuse situations in the elderly, notably in the hospital setting. In this context, active approaches such as resistance exercises and maximal voluntary contractions, which can be performed both isometrically and dynamically, are feasible during most immobilization situations including in hospitalized old people and represent powerful tools for the prevention of muscle atrophy. Aerobic exercise should also be prescribed whenever possible to reduce the loss of cardiovascular capacity associated with disuse periods. Other feasible strategies for patients who are unwilling or unable to perform volitional exercise comprise neuromuscular electrical stimulation, vibration, and blood flow restriction. However, they should ideally be applied synchronously with voluntary exercise to obtain synergistic benefits.
Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Transtornos Musculares Atróficos/prevenção & controle , Transtornos Musculares Atróficos/fisiopatologia , Idoso , Animais , Humanos , Contração Muscular/fisiologia , Músculo Esquelético/patologia , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Atrofia Muscular/prevenção & controle , Transtornos Musculares Atróficos/diagnósticoRESUMO
The contralateral effects of unilateral strength training, known as cross-education of strength, date back well over a century. In the last decade, a limited number of studies have emerged demonstrating the preservation or "sparing" effects of cross-education during immobilization. Recently published evidence reveals that the sparing effects of cross-education show muscle site specificity and involve preservation of muscle cross-sectional area. The new research also demonstrates utility of training with eccentric contractions as a potent stimulus to preserve immobilized limb strength across multiple modes of contraction. The cumulative data in nonclinical settings suggest that cross-education can completely abolish expected declines in strength and muscle size in the range of â¼13% and â¼4%, respectively, after 3-4 weeks of immobilization of a healthy arm. The evidence hints towards the possibility that unique mechanisms may be involved in preservation effects of cross-education, as compared with those that lead to functional improvements under normal conditions. Cross-education effects after strength training appear to be larger in clinical settings, but there is still only 1 randomized clinical trial demonstrating the potential utility of cross-education in addition to standard treatment. More work is necessary in both controlled and clinical settings to understand the potential interaction of neural and muscle adaptations involved in the observed sparing effects, but there is growing evidence to advocate for the clinical utility of cross-education.
Assuntos
Força Muscular/fisiologia , Transtornos Musculares Atróficos , Treinamento Resistido , Restrição Física/efeitos adversos , Braço/fisiopatologia , Traumatismos do Braço/reabilitação , Traumatismos do Braço/terapia , Humanos , Transtornos Musculares Atróficos/etiologia , Transtornos Musculares Atróficos/fisiopatologia , Transtornos Musculares Atróficos/prevenção & controleRESUMO
The aim of this study was to clarify the mechanism of disuse-induced muscle hyperalgesia through the evaluation of the pharmacological behaviour of muscle hyperalgesia profiles in chronic post-cast pain (CPCP) rats with acute and chronic-phase mirror-image muscle hyperalgesia treated with diclofenac (NSAID), pregabalin (an inhibitor of Ca2+ channel α2δ), and duloxetine (SNRI). After 2 weeks of cast immobilization, the peak cross-sectional area and muscle wet weight of the ipsilateral soleus and gastrocnemius muscles decreased more significantly in CPCP rats than in untreated rats. Histological findings revealed disuse-induced muscle atrophy in CPCP rats. The blood biochemical parameters of CPCP rats in acute and chronic phases did not differ significantly from those of untreated rats. The diclofenac and pregabalin-treated groups exhibited no improvement in acute or chronic muscle hyperalgesia. In contrast, the duloxetine-treated group exhibited an improvement in acute muscle hyperalgesia, but showed no apparent effect on chronic muscle hyperalgesia on ipsilateral or contralateral sides. However, the chronic muscle hyperalgesia was reversed by intrathecal administration of DAMGO (a µ-opioid receptor agonist). The results suggest that chronic muscle hyperalgesia in CPCP rats did not result from an inflammatory mechanism, and there is only a low probability that it's caused by a neuropathic mechanism.
Assuntos
Dor Crônica/tratamento farmacológico , Diclofenaco/administração & dosagem , Cloridrato de Duloxetina/administração & dosagem , Dor Musculoesquelética/tratamento farmacológico , Pregabalina/administração & dosagem , Animais , Dor Crônica/fisiopatologia , Modelos Animais de Doenças , Humanos , Músculo Esquelético/efeitos dos fármacos , Transtornos Musculares Atróficos/fisiopatologia , Transtornos Musculares Atróficos/prevenção & controle , Dor Musculoesquelética/fisiopatologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.
Assuntos
Alopurinol/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Transtornos Musculares Atróficos/tratamento farmacológico , Animais , Traumatismos do Tornozelo/tratamento farmacológico , Traumatismos do Tornozelo/fisiopatologia , Elevação dos Membros Posteriores , Humanos , Camundongos , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Transtornos Musculares Atróficos/fisiopatologia , Condicionamento Físico Animal , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Ubiquitina/genéticaRESUMO
INTRODUCTION: The effects of spinal bulbar muscular atrophy (SBMA) on quality of life (QoL) are not well understood. This study describes symptoms from the patient's perspective and the impact these symptoms have on QoL. METHODS: We conducted open-ended interviews with 21 adult men with genetically confirmed SBMA. Using a qualitative framework technique, we coded and analyzed interviews to identify symptoms and resulting themes. RESULTS: From these interviews, 729 quotations were extracted. We identified 200 SBMA-specific symptoms and 20 symptomatic themes. Weakness was mentioned by all interviewees. Symptoms within the domain of mental health and the specific themes of emotional issues and psychological impact were also frequently mentioned. DISCUSSION: Numerous symptoms affect QoL for patients with SBMA. We identified previously unrecognized symptoms that are important to address in enhancing clinical care for patients with SBMA and in developing tools to evaluate efficacy in future clinical trials. Muscle Nerve 57: 40-44, 2018.
Assuntos
Transtornos Musculares Atróficos/psicologia , Adulto , Idoso , Atitude , Emoções , Feminino , Humanos , Entrevista Psicológica , Masculino , Saúde Mental , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Debilidade Muscular/psicologia , Transtornos Musculares Atróficos/fisiopatologia , Qualidade de VidaRESUMO
The objective of this study was to determine alteration of corticospinal tract in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal controls, and then ALS were divided into two subgroups according to their clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5. The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were significantly reduced compared with normal controls, and SBMA patients. On the other hand, the mean diffusivity (MD) values were not significantly different among normal controls and the three disease groups. The rate of disease progression (ΔFRS-R) of ALS patients was significantly correlated with FA values and central motor conduction time (CMCT). In conclusion, the present study demonstrated a significant reduction of FA values in ALS patients, and the ΔFRS-R of ALS patients showed distinct regressions with FA values and CMCT, suggesting that this DTT analysis could be useful for detecting disease progression of ALS patients.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Tratos Piramidais/diagnóstico por imagem , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Anisotropia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Transtornos Musculares Atróficos/diagnóstico por imagem , Transtornos Musculares Atróficos/fisiopatologia , Condução Nervosa/fisiologia , Paraplegia/diagnóstico por imagem , Paraplegia/fisiopatologia , Estudos Retrospectivos , Estimulação Magnética TranscranianaRESUMO
This study examined the aging effect on disuse muscle atrophy prevention using heat stress. Wistar rats aged 7 and 60 weeks were divided into three groups as follows: control, immobilized (Im), and immobilized and heat stressed (ImH). Heat stress was given by immersing the hindlimbs in hot water (42 °C) for 60 min, once in every 3 days and the gastrocnemius (GAS) and soleus (SOL) muscles were extracted after 14 days. Muscle-fiber types were classified using ATPase staining. Heat shock protein 70 (HSP70) was assessed through Western blotting. In GAS muscle of both groups and SOL muscle of 7-week-old rats, the fiber diameter of each muscle type in the ImH group significantly increased compared with that in the Im group. However, this could not be observed in the SOL muscle of the 60-week-old rats. The increased percentage of type-I fibers and variability of types I and II muscle-fiber diameter were evident in the SOL muscle of the 60-week rats. HSP70 was significantly elevated in the ImH group compared with in the Im group in both muscle types of both age groups. Thus, effectiveness of heat stress in the prevention of disuse muscle atrophy appears unsatisfactory in aging muscle fibers.