bims-ensmum 2026-10-18 papers

bims-ensmum

Biomed News

on Exercise and nutrition in skeletal muscle metabolism

Issue of 2026–10–18
seven papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht

Differential alternative splicing in skeletal muscle after 14 days immobilization-induced atrophy in young men.
Aging concomitantly reduces skeletal muscle proteome plasticity and hypertrophic responses to resistance training in male adults.
Stable isotope-derived measurements of protein synthesis detect amino acid-induced anabolism in skeletal muscle microtissues not captured by puromycin labelling.
Redox resilience in skeletal muscle aging: cellular adaptations and exercise-mediated homeostasis.
Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.
Exercise-Induced Dehydration Limits the Effectiveness of Post-Exercise Whey Protein Supplementation in Healthy Young Men.
Blood Flow Restriction Accelerates the Onset of Neuromuscular Fatigue, Anaerobic Metabolism, and Maximal Oxygen Uptake.

Pflugers Arch. 2026 Oct 12. pii: 90. [Epub ahead of print]478(11):

Differential alternative splicing in skeletal muscle after 14 days immobilization-induced atrophy in young men.

Aliah Y Aziz, Jamie-Lee M Thompson, Thomas M Doering, Paul J Dunn, Vernon G Coffey.

  Skeletal muscle disuse during injury decreases muscle mass and function. Previous studies have determined differential gene expression associated with atrophy, but changes in alternative splicing (AS) in response to unloading is poorly defined. This study aimed to identify global changes in differential alternative splicing (DAS) in skeletal muscle following unloading. Twenty-one healthy males (26.0 ± 5.7 years; 81.2 ± 11.6 kg) underwent 14 days unilateral knee-brace immobilization. Participants underwent strength and muscle mass assessment before and after the immobilization and vastus lateralis muscle biopsies were taken pre-immobilization, and on days 3 and 14. RNA-sequencing was performed, and DAS events were identified using the rMATS package. Leg strength decreased - 21.5 kg (P < 0.0001) while mid-thigh circumference was reduced ~ 2% (P = 0.016). A total of 157,464 and 159,395 splicing events affecting 15,219 and 15,374 genes identified on day 3 and 14, respectively. Most DAS events occurred in coding sequence regions and were primarily due to exon skipping. A higher number of DAS events were observed by day 14 than day 3, indicating time-dependent regulation. Gene Ontology analysis of DAS at day 14 revealed 37 enriched GO biological processes related to MAPK signalling, mitochondrial function, and organelle organization. Unloading-induced atrophy was associated with widespread changes in AS, particularly in genes linked to muscle maintenance and protein synthesis. AS appears to promote down-regulation of target genes and subsequent differentially enriched biological pathways associated with the functional outcomes of decreased muscle mass and strength. These findings indicate changes in alternative splicing is a regulatory mechanism in muscle wasting during immobilization.

Keywords:  Catabolic; Disuse; Genes; Muscle wasting; Unloading

DOI:  https://doi.org/10.1007/s00424-026-03221-9
Physiol Rep. 2026 Oct;14(19): e71141

Aging concomitantly reduces skeletal muscle proteome plasticity and hypertrophic responses to resistance training in male adults.

Dustyn T Lewis, J Max Michel, Mason C McIntosh, Dakota R Tiede, Daniel L Plotkin, Madison L Mattingly, Nicholas J Kontos, George Kontos, Breanna J Mueller, Samuel C Norton, Joshua S Godwin, Brad J Schoenfeld, Melissa D Boersma, Andrew D Frugé, C Brooks Mobley, Andreas N Kavazis, Michael D Roberts.

  Resistance training (RT)-induced hypertrophy is attenuated with aging, albeit the proteomic basis of this attenuation remains unclear. We thus determined whether reduced skeletal muscle proteome plasticity accompanies age-related blunted hypertrophic responses. Seventeen younger (21.9 ± 2.5 years) and 15 older (57.5 ± 6.9 years) untrained males completed 10-12 weeks of RT, and the vastus lateralis (VL) soluble proteome was profiled pre- and post-training using data-independent acquisition mass spectrometry (2106 proteins). Despite similar training volume (p = 0.771), younger adults gained more lean body mass (+2.73 vs. +1.18 kg, p = 0.009) and VL thickness (+0.49 vs. +0.20 cm, p = 0.002) than older adults. Proteome plasticity paralleled this divergence, as RT altered 135 proteins (FDR < 0.05) in younger adults and none in older adults. This attenuation was one of magnitude rather than direction, as 81.5% of the 135 younger-adult proteins shifted concordantly in older adults (ρ = 0.711), and 75 gene sets were enriched with RT in older adults, led by translational machinery (NES up to +2.85). At baseline, 278 proteins differed between age groups (FDR <0.05), and age dominated the co-expression network (Turquoise module AUC = 0.96). In conclusion, the blunted hypertrophic response of older males coincides with a loss of RT-induced proteome plasticity, reflecting a compressed rather than qualitatively altered RT adaptation.

Keywords:  aging; hypertrophy; proteomics; resistance training; skeletal muscle

DOI:  https://doi.org/10.14814/phy2.71141
Exp Physiol. 2026 Oct 11.

Stable isotope-derived measurements of protein synthesis detect amino acid-induced anabolism in skeletal muscle microtissues not captured by puromycin labelling.

Yekaterina Tiper, Cassidy T Tinline-Goodfellow, Penney M Gilbert, Daniel R Moore.

  Skeletal muscle microtissues are valuable in vitro models for studying the stimuli regulating muscle protein synthesis (MPS), the key determinant of changes in muscle mass. Differentiated between opposing posts, microtissues contain aligned, contractile myotubes, providing a controlled system for investigating the responses of skeletal muscle to nutrient and contractile stimulation. However, microtissue MPS responses to these stimuli remain under-characterized. Stable isotope-labelled amino acid tracers deliver sarcoplasmic and myofibrillar fractional synthetic rates (FSR) for MPS in human studies but have not been implemented in engineered skeletal muscle. We close these gaps by characterizing amino acid (AA), ketone and contraction-induced MPS in 3D microtissues and 2D myotubes (without contraction) derived from the same primary myoblast line, using stable isotope tracers and puromycin incorporation. Following 4 h of AA withdrawal microtubes and myotubes underwent 2 h of acute AA and/or ketone treatment (±contraction in microtissues). In microtissues, sarcoplasmic FSR increased significantly during amino acid re-addition (P < 0.0001), whereas myofibrillar FSR displayed a main effect of condition (P = 0.0018), with an overall lesser magnitude of change compared to the sarcoplasmic fraction. However, both fractions were unresponsive to ketone stimulation, and the selected contraction regime (when combined with ketones and/or AA; all P ≥ 0.985). 2D myotubes showed significant increases in sarcoplasmic and myofibrillar FSR in response to amino acid treatment (both P ≤ 0.0003). Notably, microtissues demonstrated a more stable myofibrillar protein fraction, with a sarcoplasmic-to-myofibrillar FSR ratio of ∼2:1 which closely resembled that of native human muscle. The puromycin-based approach only detected subtle differences in 2D myotubes (main effect P = 0.031) with AA provision being greater than ketones (P = 0.0196) with no other post hoc differences (all P ≥ 0.221). Puromycin failed to detect MPS responses to any stimulus in microtissues (all P ≥ 0.834), highlighting the greater sensitivity of tracer-based measurements, particularly where longer time scales are needed to capture an effect. These findings support the use of engineered muscle and isotope-derived measurements of MPS in future studies of stimuli regulating skeletal muscle mass.

Keywords:  anabolic stimuli; engineered skeletal muscle; protein synthesis; puromycin labelling; stable isotope tracers

DOI:  https://doi.org/10.1113/EP094100
Free Radic Biol Med. 2026 Oct 15. pii: S0891-5849(26)01214-1. [Epub ahead of print]

Redox resilience in skeletal muscle aging: cellular adaptations and exercise-mediated homeostasis.

Eva Tamayo-Torres, Miriam Martinez-Canton, Silvana Soto-Rodriguez, Abril Gorgori-Gonzalez, Julian Carretero, Juan Ignacio Cervera-Miguel, Olga Laosa, Leocadio Rodriguez-Mañas, Maria Carmen Gomez-Cabrera.

Aging progressively impairs skeletal muscle function, leading to sarcopenia, frailty, and loss of independence. Although oxidative stress has long been considered a central driver of muscle aging, increasing evidence indicates that reactive oxygen species (ROS) also serve essential signaling functions that coordinate mitochondrial remodeling, proteostasis, metabolism, and tissue repair. Consequently, age-related muscle dysfunction is increasingly understood as reflecting impaired adaptive redox signaling rather than excessive oxidant production alone. In this review, we propose the concept of redox resilience as an integrative framework describing the capacity of skeletal muscle to preserve structural integrity and functional performance through the dynamic regulation of oxidant production, antioxidant defenses, and redox-sensitive signaling in response to physiological challenges. We discuss how aging disrupts this resilience through impaired redox-sensitive signaling, including the attenuation of exercise-induced Nrf-2 activation, together with alterations in the multicellular organization of skeletal muscle. Recent advances in single-cell and single-nucleus transcriptomics have revealed that muscle aging involves profound remodeling of specialized myonuclear populations, stromal cells, immune cells, and intercellular communication networks, highlighting the multicellular complexity of skeletal muscle aging and providing a framework to investigate how redox-dependent processes may interact with tissue-wide signaling networks. We further examine how regular physical exercise reinforces redox resilience by promoting transient ROS-mediated signaling through NADPH oxidases, activation of Nrf-2 and PGC-1α-dependent pathways, mitochondrial quality control, and metabolic remodeling. These adaptations enhance the capacity of skeletal muscle to respond to physiological stress while preserving tissue homeostasis. Finally, we discuss future perspectives for targeting adaptive redox networks to promote healthy muscle aging and propose that restoring redox resilience may preserve physiological ROS signaling while strengthening endogenous antioxidant responses and limiting excessive oxidative damage, thereby contributing to the maintenance of muscle function and health span.

DOI: https://doi.org/10.1016/j.freeradbiomed.2026.10.023
Nat Metab. 2026 Oct 12.

Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.

Nigel Kurgan, Jeppe Kjærgaard, Naja Zenius Jespersen, Virginia Díez-Obrero, Victor Svenstrup, Roger Moreno-Justicia, Sarah Elizabeth Heywood, Cecilie Bergmann Lindqvist, Lisa Ottander, Diana Samodova-Sommer, Alina Malita, Olga Kubrak, Nadja Ahrentløv, Nina Sloth Nielsen, Cody Garett Durrer, Michael Texada, Mathias Ried-Larsen, Simon Rasmussen, Kim Rewitz, Ruth J F Loos, Roelof Adriaan Johan Smit, Bente Klarlund Pedersen, Atul Shahaji Deshmukh.

Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas ( https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/ ) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines.

DOI: https://doi.org/10.1038/s42255-026-01621-w
Nutrients. 2026 Oct 04. pii: 3267. [Epub ahead of print]18(19):

Exercise-Induced Dehydration Limits the Effectiveness of Post-Exercise Whey Protein Supplementation in Healthy Young Men.

Zekun Xin, Mengtong Gao, Xinjie Wu, Min See, Peng Cheng, Yi Yan.

   BACKGROUND/OBJECTIVES: Post-exercise protein ingestion is widely used to promote recovery from exercise, but whether exercise-induced dehydration limits the subsequent protein supplementation response remains unclear. This study examined the effects of different hydration strategies during exercise on post-exercise whey protein supplementation.
METHODS: Thirteen healthy young men completed three partially crossover trials designed to produce approximately 2% (DEH: a dehydration trial without fluid replacement), 1% (EUH_50%: a 50% fluid-replacement trial), and 0% (EUH: a euhydration trial with 100% fluid replacement) body mass loss. Within 5 min after each exercise, participants ingested 45 g of whey protein dissolved in 450 mL of water. Serum amino acid concentrations were measured before exercise, immediately after exercise, and at 60 and 120 min after ingestion.
RESULTS: The protocol produced distinct exercise hydration status, with body mass loss of 2.20 ± 0.19% (DEH), 1.18 ± 0.30% (EUH_50%), and 0.27 ± 0.35% (EUH), respectively. Post-exercise whey protein ingestion increased serum amino acid concentrations in all trials. However, at 60 min after ingestion, the DEH trial showed lower total amino acid, branched-chain amino acid, leucine, isoleucine, and glutamine concentrations than both EUH_50% and EUH (all p < 0.05). The 0-120 min percentage incremental area under the curve for total amino acids, branched-chain amino acids, isoleucine, and glutamine was also lower in DEH. Gastrointestinal symptoms remained low across all conditions, with only 1.0% of individual item scores exceeding 4.
CONCLUSIONS: These findings indicate that exercise-induced hypohydration of approximately 2.2% body mass attenuates the early circulating amino acid response to post-exercise whey protein ingestion, suggesting that inadequate fluid intake during exercise may compromise the efficacy of whey protein supplementation for post-exercise recovery.

Keywords:  branched-chain amino acids; exercise-induced dehydration; fluid restriction; serum amino acids; whey protein

DOI:  https://doi.org/10.3390/nu18193267
Med Sci Sports Exerc. 2026 Oct 12.

Blood Flow Restriction Accelerates the Onset of Neuromuscular Fatigue, Anaerobic Metabolism, and Maximal Oxygen Uptake.

Sean M Lubiak, Mason A Howard, Jeffrey T Schmidt, David H Fukuda, Jeffrey R Stout, Joshua L Keller, Ethan C Hill.

   PURPOSE: Prescribing aerobic exercise with blood flow restriction (BFR) relative to physical working capacity at the fatigue threshold (PWCFT), gas exchange threshold (GET), respiratory compensation point (RCP), or maximal oxygen uptake (V̇O2max) derived from an incremental exercise test without BFR may inaccurately estimate exercise intensity. The purpose of this investigation was to examine the acute effects of an incremental cycling test performed with and without BFR on PWCFT, GET, RCP, and V̇O2max.
METHODS: Eighteen aerobically trained females completed an incremental cycling test and a verification bout with and without BFR on separate visits. Each test began with a five-minute warmup at 50 watts (W) and a cadence of 70 revolutions per minute. Following this, the test began at 50 W and increased by 30 W every two minutes until volitional failure. To apply BFR during the incremental protocol, pneumatic cuffs were placed bilaterally to the upper thighs after the warmup. Separate Bayesian paired samples t-tests were performed and are reported as a meaningful difference if the 95% high-density interval (95% HDI) did not include zero.
RESULTS: Applying BFR decreased PWCFT (95% HDI: 28.0 to 46.4 W), decreased V̇O2 at GET (95% HDI: 104.0 to 307.0 mL˙min -1), decreased V̇CO2 at GET (95% HDI: 115.0 to 347.0 mL˙min -1), decreased V̇O2 at RCP (95% HDI: 257.0 to 403.0 mL˙min -1), decreased V̇CO2 at RCP (95% HDI: 329.0 to 525.0 mL˙min -1), and decreased V̇O2max (95% HDI: 374.0 to 470.0 mL˙min -1) relative to the unrestricted incremental cycling test.
CONCLUSIONS: These responses suggest that BFR accelerated the recruitment of higher threshold motor units, induced earlier shifts to the heavy and severe exercise domains, and expedited the plateau in maximal oxygen uptake.

Keywords:  AEROBIC EXERCISE; FEMALE; GAS EXCHANGE THRESHOLD; OCCLUSION

DOI:  https://doi.org/10.1249/MSS.0000000000004189