Cardiomyocyte PGC-1α enables physiological adaptations to endurance exercise through suppression of GDF15 and cardiac atrophy DOI Open Access
Sumeet A. Khetarpal, Haobo Li, Tevis Vitale

et al.

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

Published: Feb. 2, 2024

Summary Exercise training induces physiological cardiac hypertrophy, enhanced mitochondrial biogenesis and myocardial contractility. In skeletal muscle, the transcriptional coactivator PGC-1α is a key orchestrator of these responses. The heart expresses abundant exercise-responsive PGC-1α, but it unclear whether cardiomyocyte necessary for adaptation to endurance training. Here we demonstrate that required hypertrophy during exercise in mice. absence voluntary wheel running does not improve capacity instead confers immune-fibrotic-atrophic failure after just 6 weeks We identify as negative regulator stress-responsive senescence gene expression. most enriched myomitokine GDF15. GDF15 secreted locally systemically PGC-1α-deficient mouse hearts reduces size. Cardiomyocyte-specific reduction expression preserves tolerance contractility mice Finally, show PPARGC1A correlates with number negatively human cardiomyopathies through single nucleus RNA sequencing. Our data implicate vital safeguard against stress-induced atrophy local GDF15-induced dysfunction exercise.

Language: Английский

Mitochondrial heterogeneity and adaptations to cellular needs DOI
Melia Granath-Panelo, Shingo Kajimura

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 674 - 686

Published: May 1, 2024

Language: Английский

Citations

18
Immunological regulation of skeletal muscle adaptation to exercise DOI
P. Kent Langston, Diane Mathis

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1175 - 1183

Published: April 25, 2024

Language: Английский

Citations

10
The role of skeletal muscle respiratory capacity in exercise performance DOI Creative Commons
Pablo M. García-Rovés,

Jorge Alvarez-Luis,

Sandra Cutanda-Tesouro

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST DOI
Hans‐Georg Sprenger, Melanie J. Mittenbühler, Yizhi Sun

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training DOI Creative Commons
Mark Viggars,

Hannah E Berko,

Stuart J. Hesketh

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 86, P. 101980 - 101980

Published: June 29, 2024

In this investigation, we addressed the contribution of core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses exercise and remodeling response training. Additionally, adopted a systems biology approach investigate how loss BMAL1 altered peripheral tissue homeostasis as well training adaptations iWAT, liver, heart, lung male mice.

Language: Английский

Citations

7
Molecular aspects of the exercise response and training adaptation in skeletal muscle DOI Creative Commons
Regula Furrer, Christoph Handschin

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 53 - 68

Published: July 24, 2024

Skeletal muscle plasticity enables an enormous potential to adapt various internal and external stimuli perturbations. Most notably, changes in contractile activity evoke a massive remodeling of biochemical, metabolic force-generating properties. In recent years, large number signals, sensors, regulators effectors have been implicated these adaptive processes. Nevertheless, our understanding the molecular underpinnings training adaptation remains rudimentary. Specifically, mechanisms that underlie signal integration, output coordination, functional redundancy other complex traits are unknown. fact, it is even unclear how stimulus-dependent specification brought about endurance or resistance exercise. this review, we will provide overview on events describe acute perturbations single exercise bouts. Furthermore, insights into principles long-term adaptation. Finally, current gaps knowledge be identified, strategies for multi-omic –cellular analyses skeletal engaged individual, bouts chronic discussed.

Language: Английский

Citations

7
Methylome–proteome integration after late‐life voluntary exercise training reveals regulation and target information for improved skeletal muscle health DOI Creative Commons
Toby L. Chambers, Andrea Dimet‐Wiley, Alexander R. Keeble

et al.

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

Citations

7
The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth DOI Creative Commons
Sebastian Edman,

Ronald G. Jones,

Paulo R. Jannig

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Language: Английский

Citations

6
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 DOI Creative Commons
Sebastian Edman,

Ronald G. Jones,

Paulo R. Jannig

et al.

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

Published: March 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.

Language: Английский

Citations

4
An Integrated Neuromuscular Training Intervention Applied in Primary School Induces Epigenetic Modifications in Disease‐Related Genes: A Genome‐Wide DNA Methylation Study DOI Creative Commons
Fidanka Vasileva, Raquel Font‐Lladó, Víctor López‐Ros

et al.

Scandinavian Journal of Medicine and Science in Sports, Journal Year: 2025, Volume and Issue: 35(1)

Published: Jan. 1, 2025

Physical exercise has been shown to induce epigenetic modifications with various health implications, directly affect DNA methylation (DNAm), as well reverse the age. Hence, we aimed identify differential changes and assess age in saliva of 7-9-year-old school children following a 3-month integrated neuromuscular training (INT), explore if any are core genes. Core genes defined high relevance essential importance within human genome. Forty (17 boys 23 girls) were recruited from schools Girona, Spain, allocated into control (N = 20) or INT group. The group performed warm-up during physical education (PE) classes, encompassing strength, coordination, dynamic stabilization, plyometrics, speed, agility exercises, whereas traditional activities, aerobic exercises that will prepare cardiovascular system increase joint mobility for upcoming effort class. Genome-wide DNAm analysis was Illumina 900 K microarray. recognized based on accomplishment rigorous widely accepted 3-point criteria: participation enriched pathways, connectivity (≥ 10), target key transcription factors. There 1200 differentially methylated positions (DMPs) 414 DMPs (FDR < 0.05, p Aβ |0.1|), suggesting non-significant trend acceleration (1.18 months, > 0.05) 1-month decrease (p 0.05). showed low similarity between pathways interconnectivity, distinct mostly development growth-related. Additionally, no identified Interestingly, related involving signaling mechanisms, hormone protein metabolism pathways. Moreover, 17 main findings present study an response stimulus INT, including considered Trial Registration: protocol registered ISRCTN registry (ISRCTN16744821).

Language: Английский

Citations

0