Methylome–proteome integration after late‐life voluntary exercise training reveals regulation and target information for improved skeletal muscle health

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 603(1), P. 211 - 237

Published: July 26, 2024

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on in preclinical setting, we developed combined endurance-resistance training mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics promotes aspects partial epigenetic reprogramming when performed late life (22-24 months age). In this investigation, leveraged pan-mammalian DNA methylome arrays tandem mass-spectrometry proteomics to provide detailed information late-life adaptations female relative age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related transcriptional regulation genes as well Nr4a3, Hes1 Hox after PoWeR. Using holistic method -omics integration binding expression target analysis (BETA), changes were associated with upregulated proteins global mitochondrial translation (P 0.03). Specifically, BETA implicated control ribosomal, mitoribosomal, complex I protein abundance training. may also influence LACTB, MIB1 UBR4 induction - all are mechanistically linked health. Computational cistrome predicted several transcription factors including MYC regulators trained methylome-proteome landscape, corroborating prior transcriptome data. Correlating proteome mass fatigue resistance revealed positive relationships VPS13A NPL levels, respectively. Our findings expose differential proteomic translational that could function aged mice. KEY POINTS: Late-life from 22-24 age shown improve vivo promote mitigation. Integration 36k using (which contain ageing clock sites) exploratory extends our work reveals coordinated widespread initiation, ribosomal (mitoribosomal) voluntary sizeable cohort group analysis). Multi-omics serine β-lactamase-like (LACTB tumour muscle), mind bomb 1 (MIB1 satellite cell type 2 fibre maintenance) ubiquitin ligase E3 component N-recognin 4 (UBR4 quality control) identified regulator proteome, agreement analyses. Vacuolar sorting 13 homolog A (VPS13A) positively correlated mass, glycoprotein/glycolipid sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) resistance.

Language: Английский

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Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8959 - 8959

Published: Aug. 17, 2024

Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one triggering events in weaknesses old age. Prominent structural and functional alterations NMJs were described elderly rodents, but NMJ changes middle age remain unclear. Here, we compared muscles from young adult (3 months) middle-aged (12 BALB/c mice. Microelectrode recordings, immunofluorescent staining, electron microscopy, myography, whole-body plethysmography used. We revealed presynaptic (i) postsynaptic (ii) changes. The former included an increase both action potential propagation velocity neurotransmitter release evoked by low-, moderate-, high-frequency activity a decrease immunoexpression synapsin 1 synaptic vesicle clustering. latter consisted currents via nicotinic acetylcholine receptors area their distribution. These correlated with increased contractile responses to moderate- nerve activation. Additionally, found pattern respiration (an peak inspiratory flow tendency elevation tidal volume), which imply conclude that enhancement neuromuscular communication (due mechanism) accompanied improved occurs early aging.

Language: Английский

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Physiology of ageing skeletal muscle and the protective effects of exercise

The Journal of Physiology, Journal Year: 2025, Volume and Issue: 603(1), P. 3 - 6

Published: Jan. 1, 2025

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Language: Английский

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Physiological mechanisms of neuromuscular impairment in diabetes‐related complications: Can physical exercise help prevent it?

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Diabetes mellitus is a chronic disorder that progressively induces complications, compromising daily independence. Among these, diabetic neuropathy particularly prevalent and contributes to substantial neuromuscular impairments in both types 1 2 diabetes. This condition leads structural damage affecting the central peripheral nervous systems, resulting significant decline sensorimotor functions. Alongside neuropathy, myopathy also muscle impairment reduced motor performance, intensifying decline. Diabetic typically implicates neurogenic atrophy, motoneuron loss clustering of fibres as result aberrant denervation-reinervation processes. These complications are associated with compromised junctions, where alterations occur pre-synaptic vesicles, mitochondrial content post-synaptic signalling. Neural intensified by hyperglycaemia oxidative stress, exacerbating vascular dysfunction reducing oxygen delivery. imply severe evidenced reductions maximal force power output, rate development endurance. Furthermore, diabetes-related compounded age-related degenerative changes long-term patients. Aerobic resistance training offer promising approaches for managing blood glucose levels function. exercise promotes biogenesis angiogenesis, supporting metabolic cardiovascular health. Resistance primarily enhances neural plasticity, strength hypertrophy, which crucial factors mitigating sarcopenia preserving functional topical review examines current evidence on physiological mechanisms underlying potential impact physical activity counteracting this

Language: Английский

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Neuromuscular electrical stimulation training induces myonuclear accretion and hypertrophy in mice without overt signs of muscle damage and regeneration

Skeletal Muscle, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 5, 2025

Skeletal muscle is a plastic tissue that adapts to increased mechanical loading/contractile activity through fusion of stem cells (MuSCs) with myofibers, physiological process referred as myonuclear accretion. However, it still unclear whether accretion driven by loading per se, or occurs, at least in part, response injury/regeneration. Here, we developed non-damaging protocol evaluate contractile activity-induced accretion/hypertrophy conditions. Contractile was generated applying repeated electrical stimuli over the mouse plantar flexor muscles. This method commonly NeuroMuscular Electrical Simulation (NMES) Human. Each NMES training session consisted 80 isometric contractions delivered ∼15% maximal tetanic force avoid damage. C57BL/6J male mice were submitted either short (i.e., 6 sessions) long 12 individualized program while unstimulated used controls. Histological investigations performed assess impact on MuSC number and status, myonuclei content integrity, typology size. led robust proliferation MuSCs absence overt signs damage/regeneration. NMES-induced specific type IIB myofibers an early event preceding hypertrophy inasmuch mild increase myofiber cross-sectional area only observed long-term protocol. We conclude are injury.

Language: Английский

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Mature and Juvenile Neuromuscular Plasticity in Response to Unloading

Developmental Neurobiology, Journal Year: 2025, Volume and Issue: 85(3)

Published: May 8, 2025

ABSTRACT The neuromuscular junction (NMJ) is the synapse that enables requisite electrical communication between motor nervous system and myofibers respond to such stimulation with movement force development. Changes in an NMJ's normal activity pattern have been demonstrated remodel both comprise NMJ. Significant amounts of research devoted study aging on system. Far less, however, has focused revealing effects reduced NMJ comprising juvenile systems. In present investigation, consequences decreased imposed by muscle unloading (UL) via hindlimb suspension for 2 weeks (a period known induce remodeling) were examined young adult, is, mature (8 mo), (3 mo) total, 4 treatment groups comprised 10 animals (Juvenile‐Control, Juvenile‐Unloaded, Mature‐Control, Mature‐Unloaded) studied. Immunofluorescent procedures, coupled confocal microscopy, used quantify remodeling pre‐ postsynaptic features NMJs, as well assessing myofiber profiles soleus muscles housing NMJs interest. Results ANOVA procedures revealed there significant ( p < 0.05) main treatment, whereby UL consistently led expanded size NMJ, Age where dimensions linked compared Moreover, only sporadically was interaction Treatment noted. Importantly, one variable remained impressively resistant critical parameter coupling suggesting stability effective at throughout lifespan despite changes patterns. data presented here suggest further inquiry must be performed regarding disuse‐related plasticity adolescent individuals those regularly suffer injuries resulting periods UL.

Language: Английский

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Functions require junctions: endurance exercise protects from age‐induced alterations of the neuromuscular system

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 603(1), P. 37 - 39

Published: March 26, 2024

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Language: Английский

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Longitudinal Decline of Exercise Capacity in Male and Female Mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

The population of older adults is exponentially expanding. Alongside aging comes the onset chronic disease, decline functional capacity, and reduced quality life. Thus, this increase will stress capacity financial viability health long-term care systems. Developing pre-clinical models for age-related imperative to advancing therapies that extend healthspan prolong independence. Previously in a cross-sectional study, we established powerful composite scoring system termed CFAB (comprehensive assessment battery). measures physical function exercise using well-validated determinants measure overall motor function, fore-limb strength, four-limb strength/endurance, aerobic volitional exercise/activity rate. In current work, used track cohorts male female C57BL/6 mice over lifespan (measuring at 6, 12, 18, 24, 28 months age). Overall, found statistically significantly declining as aged, with some differences between males females trajectory slope. We also determined body mass changes presented differently sexes, tracked composition (fat percentage, magnetic resonance imagery) females. subset mice,

Language: Английский

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Mitochondrial disorders are associated with morphological neuromuscular junction defects

Neuromuscular Disorders, Journal Year: 2024, Volume and Issue: 45, P. 105235 - 105235

Published: Oct. 25, 2024

Language: Английский

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