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

The Journal of Physiology, Год журнала: 2024, Номер 603(1), С. 211 - 237

Опубликована: Июль 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.

Язык: Английский

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The utility of the rodent synergist ablation model in identifying molecular and cellular mechanisms of skeletal muscle hypertrophy

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C601 - C606

Опубликована: Июль 29, 2024

Skeletal muscle exhibits remarkable plasticity to adapt stimuli such as mechanical loading. The mechanisms that regulate skeletal hypertrophy due overload have been thoroughly studied. Remarkably, our understanding of many the molecular and cellular hypertrophic growth were first identified using rodent synergist ablation (SA) model subsequently corroborated in human resistance exercise training studies. To demonstrate utility SA model, we briefly summarize following translation these mechanism induced by training.

Язык: Английский

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The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

EMBO Reports, Год журнала: 2024, Номер unknown

Опубликована: Окт. 31, 2024

Язык: Английский

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The rRNA epitranscriptome and myonuclear SNORD landscape in skeletal muscle fibers contributes to ribosome heterogeneity and is altered by hypertrophic stimulus

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C516 - C524

Опубликована: Июнь 24, 2024

Ribosomal RNAs (rRNAs) are posttranscriptionally modified by 2′ O-methyl (2′- O-Me). This study applied RiboMeth-seq (RMS) to detect changes in 2′- O-Me levels during skeletal muscle hypertrophy, uncovering transient diversification of the ribosome pool fibers. work implies a role for heterogeneity growth and adaptation.

Язык: Английский

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The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 27, 2024

Abstract Molecular control of recovery after exercise in muscle is temporally dynamic. A time course biopsies around resistance (RE) combined with -omics necessary to better comprehend the molecular contributions skeletal adaptation humans. Vastus lateralis before and 30 minutes, 3-, 8-, 24-hours acute RE were collected. time-point matched biopsy-only group was also included. RNA-sequencing defined transcriptome while DNA methylomics computational approaches complemented these data. The post-RE revealed: 1) methylome responses at minutes corresponded upregulated genes 3 hours, 2) a burst translation- transcription-initiation factor-coding transcripts occurred between 8 3) global gene expression peaked 4) ribosome-related dominated mRNA landscape 24 5) methylation-regulated MYC highly influential transcription factor throughout 24-hour played primary role levels hours. influence human strengthened by information from overexpression mouse muscle. To test whether sufficient for hypertrophy, we generated fiber-specific doxycycline inducible model pulsatile induction. Periodic 48-hour pulses over 4 weeks resulted higher mass fiber size soleus adult female mice. Collectively, present resolved resource understanding adaptations reveal as regulator RE-induced hypertrophy.

Язык: Английский

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Skeletal muscle hypertrophy: cell growth is cell growth

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C614 - C618

Опубликована: Июль 29, 2024

Roberts et al. have provided an insightful counterpoint to our review article on the utility of synergist ablation model. The purpose this is provide some further dialogue regarding strengths and weaknesses Specifically, we highlight that robustness model overshadows surgical limitations. We also compare transcriptomic responses in mice resistance exercise humans identify common pathways. conclude "cell growth cell growth" mechanisms available cells accumulate biomass increase size are similar across types independent rate growth.

Язык: Английский

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miRNA‐1 regulation is necessary for mechanical overload‐induced muscle hypertrophy in male mice

Physiological Reports, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 1, 2025

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in regulating gene expression post‐transcriptionally. They involved various developmental and physiological processes, their dysregulation is linked to diseases. Skeletal muscle‐specific miRNAs, including miR‐1, crucial the development maintenance of skeletal muscle. It has been demonstrated miR‐1 decreases by approximately 50% response hypertrophic stimuli, suggesting its potential involvement muscle hypertrophy. In our study, we hypothesize reduction levels necessary for growth due interaction essential pro‐growth genes. Promoting smaller levels, observed blunted mice undergoing murine model addition, results suggest inhibits Itm2a , membrane‐related protein, as miR‐1‐related candidate While exact mechanism hypertrophy not identified, miR‐1‐regulated membrane proteins important

Язык: Английский

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At the Nexus Between Epigenetics and Senescence: The Effects of Senolytic (BI01) Administration on DNA Methylation Clock Age and the Methylome in Aged and Regenerated Skeletal Muscle

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

ABSTRACT Senescent cells emerge with aging and injury. The contribution of senescent to DNA methylation age (DNAmAGE) in vivo is uncertain. Furthermore, stem cell therapy can mediate “rejuvenation”, but how tissue regeneration controlled by resident affects whole DNAmAGE unclear. We assessed or without senolytics (BI01) aged male mice (24–25 months) 35 days following muscle healing (BaCl 2 ‐induced versus non‐injured). Young injured (5–6 were comparators. was decelerated up 68% after injury muscle. modestly further significantly recovery senolytics. ~1/4 measured CpGs altered then regardless Specific changes caused included differential regulation Col , Hdac Hox Wnt genes, which likely contributed improved regeneration. Altered extracellular matrix remodeling using histological analysis aligned the methylomic findings Without senolytics, had a contrasting effect young tended not influence accelerate DNAmAGE. Comparing old methylome‐transcriptome integration, we found more coordinated molecular profile genes implicated performance: Axin2 Egr1 Fzd4 Meg3 Spry1 . Muscle affect influences transcriptomic‐methylomic landscape cell‐driven reformation. Our data have implications for understanding plasticity developing therapies aimed at collagen senescence.

Язык: Английский

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A primer on global molecular responses to exercise in skeletal muscle: Omics in focus

Journal of sport and health science/Journal of Sport and Health Science, Год журнала: 2025, Номер unknown, С. 101029 - 101029

Опубликована: Фев. 1, 2025

Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level. Over past 2 decades, transcriptome studies have detailed acute and chronic responses to resistance, endurance, concurrent exercise, focusing on variables such as training status, nutrition, age, sex, metabolic health profile. Multi-omics approaches, integration transcriptomic epigenetic data, along with emerging ribosomal RNA sequencing advancements, further provided insights into how adapts exercise across lifespan. Downstream transcriptome, proteomic phosphoproteomic identified novel regulators adaptations, while single-cell/nucleus spatial technologies promise evolve cellular specialization communication around cells. This narrative review highlights (a) historical foundations muscle, (b) current research 3 layers cascade (DNA, RNA, protein), (c) applications single-cell study adaptation exercise. Further elaboration muscle's global footprint using multi-omics methods will help researchers practitioners develop more effective targeted approaches improve well athletic performance.

Язык: Английский

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The utility—and limitations—of the rodent synergist ablation model in examining mechanisms of skeletal muscle hypertrophy

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C607 - C613

Опубликована: Июль 29, 2024

In this issue, Burke et al. discuss the utility of rodent synergist ablation (SA) model for examining mechanisms associated with skeletal muscle hypertrophy. invited perspective, we aim to complement their original perspective by discussing limitations along alternative mechanical overload models that have strengths and limitations.

Язык: Английский

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