Pub Date : 2025-01-01Epub Date: 2024-12-30DOI: 10.1113/JP286205
Gustavo Balbinot, Matija Milosevic, Cindi M Morshead, Stephanie N Iwasa, Jose Zariffa, Luka Milosevic, Taufik A Valiante, Joaquín Andrés Hoffer, Milos R Popovic
The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour. Here we examine the neural mechanisms that are thought to underlie the therapeutic effects seen with current neuromodulation technologies. To gain further insights into the mechanisms associated with electrical stimulation, we summarize recent findings from genetic dissection studies conducted in animal models. KEY POINTS: Electricity is everywhere around us and is essential for how our nerves communicate within our bodies. When nerves are damaged or not working properly, using exogenous electricity can help improve their function at distinct levels - inside individual cells, within neural circuits, and across entire systems. This method can be tailored to target specific types of cells, nerve fibres, neurotransmitters and communication pathways, offering significant therapeutic potential. This overview explains how exogenous electricity affects nerve function and its potential benefits, based on research in animal studies. Understanding these effects is important because electrical neuromodulation plays a key role in medical treatments for neurological conditions.
{"title":"The mechanisms of electrical neuromodulation.","authors":"Gustavo Balbinot, Matija Milosevic, Cindi M Morshead, Stephanie N Iwasa, Jose Zariffa, Luka Milosevic, Taufik A Valiante, Joaquín Andrés Hoffer, Milos R Popovic","doi":"10.1113/JP286205","DOIUrl":"10.1113/JP286205","url":null,"abstract":"<p><p>The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour. Here we examine the neural mechanisms that are thought to underlie the therapeutic effects seen with current neuromodulation technologies. To gain further insights into the mechanisms associated with electrical stimulation, we summarize recent findings from genetic dissection studies conducted in animal models. KEY POINTS: Electricity is everywhere around us and is essential for how our nerves communicate within our bodies. When nerves are damaged or not working properly, using exogenous electricity can help improve their function at distinct levels - inside individual cells, within neural circuits, and across entire systems. This method can be tailored to target specific types of cells, nerve fibres, neurotransmitters and communication pathways, offering significant therapeutic potential. This overview explains how exogenous electricity affects nerve function and its potential benefits, based on research in animal studies. Understanding these effects is important because electrical neuromodulation plays a key role in medical treatments for neurological conditions.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"247-284"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-12-20DOI: 10.1113/JP287448
Seyed Mohammadali Rahmati, Alexander N Klishko, Ramaldo S Martin, Nate E Bunderson, Jeswin A Meslie, T Richard Nichols, Ilya A Rybak, Alain Frigon, Thomas J Burkholder, Boris I Prilutsky
Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from six cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA) and fascicle length. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in seven and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle's moment arm, PCSA and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibres (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii length afferents matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion. KEY POINTS: Little is known about the role of forelimb muscle morphology in producing motor outputs and generating somatosensory signals. This information is needed to understand the contributions of forelimbs in locomotor control. We measured morphological characteristics of 46 muscles from cat forelimbs, recorded cat walking mechanics and electromyographic activity, and computed patterns of moment arms, length, velocity, activation, and force of forelimb muscles, as well as length- and force-dependent afferent activity during walking. We demonstrated that moment arms, physiological cross-sectional area and fascicle length of forelimb muscles contribute substantially to muscle force production and proprioceptive activity, to the regulation of locomotor cycle phase transitions and to control of lateral stability. The obtained information can guide the development of biologically accurate neuromechanical models of quadrupedal locomotion for exploring and testing novel methods of treatments of central nervous system pathologies by modulating activities in neural pathways controlling forelimbs/arms.
{"title":"Role of forelimb morphology in muscle sensorimotor functions during locomotion in the cat.","authors":"Seyed Mohammadali Rahmati, Alexander N Klishko, Ramaldo S Martin, Nate E Bunderson, Jeswin A Meslie, T Richard Nichols, Ilya A Rybak, Alain Frigon, Thomas J Burkholder, Boris I Prilutsky","doi":"10.1113/JP287448","DOIUrl":"10.1113/JP287448","url":null,"abstract":"<p><p>Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from six cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA) and fascicle length. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in seven and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle's moment arm, PCSA and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibres (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii length afferents matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion. KEY POINTS: Little is known about the role of forelimb muscle morphology in producing motor outputs and generating somatosensory signals. This information is needed to understand the contributions of forelimbs in locomotor control. We measured morphological characteristics of 46 muscles from cat forelimbs, recorded cat walking mechanics and electromyographic activity, and computed patterns of moment arms, length, velocity, activation, and force of forelimb muscles, as well as length- and force-dependent afferent activity during walking. We demonstrated that moment arms, physiological cross-sectional area and fascicle length of forelimb muscles contribute substantially to muscle force production and proprioceptive activity, to the regulation of locomotor cycle phase transitions and to control of lateral stability. The obtained information can guide the development of biologically accurate neuromechanical models of quadrupedal locomotion for exploring and testing novel methods of treatments of central nervous system pathologies by modulating activities in neural pathways controlling forelimbs/arms.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"447-487"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2023-12-05DOI: 10.1113/JP285616
Colleen L O'Reilly, Sue C Bodine, Benjamin F Miller
{"title":"Current limitations and future opportunities of tracer studies of muscle ageing.","authors":"Colleen L O'Reilly, Sue C Bodine, Benjamin F Miller","doi":"10.1113/JP285616","DOIUrl":"10.1113/JP285616","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"7-15"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-03-26DOI: 10.1113/JP286232
Leonardo Matta, Lukas Blaas, Christoph Gibis, Joel Guerra
{"title":"Functions require junctions: endurance exercise protects from age-induced alterations of the neuromuscular system.","authors":"Leonardo Matta, Lukas Blaas, Christoph Gibis, Joel Guerra","doi":"10.1113/JP286232","DOIUrl":"10.1113/JP286232","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"37-39"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-08-21DOI: 10.1113/JP287113
Lauren S Perkins, Vito A Pipitone, Jacob M Ouellette, Daniel L Scurto, Fasih A Rahman
{"title":"Considering sexually dimorphic responses to aerobic exercise in treating glucocorticoid-induced myopathy.","authors":"Lauren S Perkins, Vito A Pipitone, Jacob M Ouellette, Daniel L Scurto, Fasih A Rahman","doi":"10.1113/JP287113","DOIUrl":"10.1113/JP287113","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"41-43"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-09-19DOI: 10.1113/JP287235
Adam P Sharples
{"title":"Epigenome-proteome integration in aged skeletal muscle after exercise training.","authors":"Adam P Sharples","doi":"10.1113/JP287235","DOIUrl":"10.1113/JP287235","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"29-31"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Physiology of ageing skeletal muscle and the protective effects of exercise.","authors":"Christopher W Sundberg","doi":"10.1113/JP287926","DOIUrl":"10.1113/JP287926","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"3-6"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-07-26DOI: 10.1113/JP286681
Toby L Chambers, Andrea Dimet-Wiley, Alexander R Keeble, Amin Haghani, Wen-Juo Lo, Gyumin Kang, Robert Brooke, Steve Horvath, Christopher S Fry, Stanley J Watowich, Yuan Wen, Kevin A Murach
<p><p>Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance-resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22-24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related to transcriptional regulation genes as well as Nr4a3, Hes1 and Hox genes after PoWeR. Using a holistic method of -omics integration called binding and expression target analysis (BETA), methylome changes were associated with upregulated proteins related to global and mitochondrial translation after PoWeR (P = 0.03). Specifically, BETA implicated methylation control of ribosomal, mitoribosomal, and mitochondrial complex I protein abundance after training. DNA methylation may also influence LACTB, MIB1 and UBR4 protein induction with exercise - all are mechanistically linked to muscle health. Computational cistrome analysis predicted several transcription factors including MYC as regulators of the exercise trained methylome-proteome landscape, corroborating prior late-life PoWeR transcriptome data. Correlating the proteome to muscle mass and fatigue resistance revealed positive relationships with VPS13A and NPL levels, respectively. Our findings expose differential epigenetic and proteomic adaptations associated with translational regulation after PoWeR that could influence skeletal muscle mass and function in aged mice. KEY POINTS: Late-life combined endurance-resistance exercise training from 22-24 months of age in mice is shown to improve molecular, biochemical, cellular and in vivo functional characteristics of skeletal muscle and promote aspects of partial epigenetic reprogramming and epigenetic age mitigation. Integration of DNA CpG 36k methylation arrays using conserved sites (which also contain methylation ageing clock sites) with exploratory proteomics in skeletal muscle extends our prior work and reveals coordinated and widespread regulation of ribosomal, translation initiation, mitochondrial ribosomal (mitoribosomal) and complex I proteins after combined voluntary exercise training in a sizeable cohort of female mice (n = 7-10 per group and analysis). Multi-omics integration predicted epigenetic regulation of serine β-lactamase-like protein (LACTB - linked to tumour resistance in muscle), mind bomb 1 (MIB1 - linked to satellite cell and type 2 fibre maintenance) and ubiquitin protein ligase E3 component N-recognin 4 (UBR4 - linked to musc
运动是对抗骨骼肌老化的有效刺激。为了在临床前环境中研究运动对肌肉的影响,我们为小鼠开发了一种称为渐进负重轮跑(PoWeR)的组合耐力-阻力训练刺激。PoWeR 可改善骨骼肌的分子、生化、细胞和功能特性,并在小鼠晚期(22-24 个月)进行时促进部分表观遗传重编程。在这项研究中,我们利用泛哺乳动物 DNA 甲基组阵列和骨骼肌串联质谱蛋白质组学,提供了雌性小鼠相对于年龄匹配的静坐对照组(每组 7-10 只)的晚期 PoWeR 适应性的详细信息。PoWeR后,保守启动子位点的CpG甲基化差异与转录调控基因以及Nr4a3、Hes1和Hox基因有关。利用一种名为 "结合与表达目标分析(BETA)"的整体组学整合方法,甲基组变化与 PoWeR 后全球和线粒体翻译相关蛋白质的上调有关(P = 0.03)。具体来说,BETA 与训练后核糖体、核小体和线粒体复合体 I 蛋白丰度的甲基化控制有关。DNA 甲基化还可能影响运动后 LACTB、MIB1 和 UBR4 蛋白的诱导--所有这些都与肌肉健康有机理联系。计算序列分析预测,包括 MYC 在内的多个转录因子是运动训练甲基化组-蛋白质组格局的调节因子,这与之前的晚期 PoWeR 转录组数据相吻合。将蛋白质组与肌肉质量和抗疲劳性相关联,发现分别与 VPS13A 和 NPL 水平呈正相关。我们的研究结果揭示了 PoWeR 后与翻译调控相关的不同表观遗传和蛋白质组适应性,这可能会影响老年小鼠的骨骼肌质量和功能。关键点:小鼠从 22-24 个月大开始的晚期联合耐力-阻力运动训练可改善骨骼肌的分子、生化、细胞和体内功能特征,并促进部分表观遗传重编程和表观遗传年龄缓解。利用保守位点(也包含甲基化老化时钟位点)将 DNA CpG 36k 甲基化阵列与骨骼肌中的探索性蛋白质组学相结合,扩展了我们之前的工作,并揭示了在相当规模的雌性小鼠队列(每组 7-10 只,每项分析)中进行联合自愿运动训练后,核糖体、翻译起始、线粒体核糖体(mitoribosomal)和复合体 I 蛋白的协调和广泛调控。多组学整合预测了训练后丝氨酸β-内酰胺酶样蛋白(LACTB--与肌肉抗肿瘤有关)、心灵炸弹1(MIB1--与卫星细胞和2型纤维维持有关)和泛素蛋白连接酶E3元件N-识别素4(UBR4--与肌肉蛋白质量控制有关)的表观遗传调控。计算序列分析发现,MYC是晚年训练蛋白质组的调节因子,这与之前的转录分析结果一致。空泡蛋白分选13同源物A(VPS13A)与肌肉质量呈正相关,糖蛋白/糖脂相关的酰化酶N-乙酰神经氨酸丙酮酸裂解酶(NPL)与体内肌肉抗疲劳性相关。
{"title":"Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.","authors":"Toby L Chambers, Andrea Dimet-Wiley, Alexander R Keeble, Amin Haghani, Wen-Juo Lo, Gyumin Kang, Robert Brooke, Steve Horvath, Christopher S Fry, Stanley J Watowich, Yuan Wen, Kevin A Murach","doi":"10.1113/JP286681","DOIUrl":"10.1113/JP286681","url":null,"abstract":"<p><p>Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance-resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22-24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related to transcriptional regulation genes as well as Nr4a3, Hes1 and Hox genes after PoWeR. Using a holistic method of -omics integration called binding and expression target analysis (BETA), methylome changes were associated with upregulated proteins related to global and mitochondrial translation after PoWeR (P = 0.03). Specifically, BETA implicated methylation control of ribosomal, mitoribosomal, and mitochondrial complex I protein abundance after training. DNA methylation may also influence LACTB, MIB1 and UBR4 protein induction with exercise - all are mechanistically linked to muscle health. Computational cistrome analysis predicted several transcription factors including MYC as regulators of the exercise trained methylome-proteome landscape, corroborating prior late-life PoWeR transcriptome data. Correlating the proteome to muscle mass and fatigue resistance revealed positive relationships with VPS13A and NPL levels, respectively. Our findings expose differential epigenetic and proteomic adaptations associated with translational regulation after PoWeR that could influence skeletal muscle mass and function in aged mice. KEY POINTS: Late-life combined endurance-resistance exercise training from 22-24 months of age in mice is shown to improve molecular, biochemical, cellular and in vivo functional characteristics of skeletal muscle and promote aspects of partial epigenetic reprogramming and epigenetic age mitigation. Integration of DNA CpG 36k methylation arrays using conserved sites (which also contain methylation ageing clock sites) with exploratory proteomics in skeletal muscle extends our prior work and reveals coordinated and widespread regulation of ribosomal, translation initiation, mitochondrial ribosomal (mitoribosomal) and complex I proteins after combined voluntary exercise training in a sizeable cohort of female mice (n = 7-10 per group and analysis). Multi-omics integration predicted epigenetic regulation of serine β-lactamase-like protein (LACTB - linked to tumour resistance in muscle), mind bomb 1 (MIB1 - linked to satellite cell and type 2 fibre maintenance) and ubiquitin protein ligase E3 component N-recognin 4 (UBR4 - linked to musc","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"211-237"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-06-10DOI: 10.1113/JP285653
Yuxiao Guo, Eleanor J Jones, Thomas F Smart, Abdulmajeed Altheyab, Nishadi Gamage, Daniel W Stashuk, Jessica Piasecki, Bethan E Phillips, Philip J Atherton, Mathew Piasecki
Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex-specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low- to mid-level contractions (P < 0.05) without sex × level interactions. Females had smaller cross-sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex-specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex-based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. KEY POINTS: Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty. In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age-matched males. Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females. These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health-sex paradox.
女性的寿命通常比男性长,但矛盾的是,女性晚年的健康状况却比男性差。神经肌肉系统是走向衰弱的关键组成部分,在健康的年轻人身上,运动单位(MU)的特征因性别而异,并可能因荷尔蒙特征的不同而以性别特异性的方式适应衰老。本研究的目的是调查早期和晚期老年人肌肉外侧肌(VL)结构和功能的性别差异。研究人员收集了 50 名健康老年人(男/女:26/24)在标准亚马力收缩过程中的肌肉肌电图信号,并对信号进行分解,以量化肌肉单位的特征。同时还测量了肌肉尺寸和神经肌肉性能。女性的 MU 发火率(FR)高于男性(P = 0.025),但 MU 结构或神经肌肉接头传输(NMJ)不稳定性没有差异。从低级收缩到中级收缩,所有 MU 特性都有所增加(P = 0.025)。
{"title":"Sex disparities of human neuromuscular decline in older humans.","authors":"Yuxiao Guo, Eleanor J Jones, Thomas F Smart, Abdulmajeed Altheyab, Nishadi Gamage, Daniel W Stashuk, Jessica Piasecki, Bethan E Phillips, Philip J Atherton, Mathew Piasecki","doi":"10.1113/JP285653","DOIUrl":"10.1113/JP285653","url":null,"abstract":"<p><p>Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex-specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low- to mid-level contractions (P < 0.05) without sex × level interactions. Females had smaller cross-sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex-specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex-based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. KEY POINTS: Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty. In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age-matched males. Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females. These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health-sex paradox.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":"151-165"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Timing is everything: complex (a)synchrony of heart-muscle interactions during exercise.","authors":"Sean P Langan","doi":"10.1113/JP287967","DOIUrl":"https://doi.org/10.1113/JP287967","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}