bims-ensmum 2026-08-23 papers

bims-ensmum

Biomed News

on Exercise and nutrition in skeletal muscle metabolism

Issue of 2026–08–23
seven papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht

Ingestion of 20 g of a plant-derived protein blend with and without added leucine or whey protein does not increase muscle protein synthesis rates in older males.
Aged Mitochondrial DNA Is Associated With Aberrant Acute Exercise-Induced Redox Responses in Human Skeletal Muscle.
TDP-43 sustains satellite cells to maintain and regenerate skeletal muscle.
Analytical approaches to account for muscle size when evaluating strength.
An acute crossover trial of passive movement training with and without blood flow restriction to determine the impact on postprandial glycaemia.
Targeting TGF-β to Attenuate Ischemia-Reperfusion Associated Muscle Fibrosis and Enhance Regeneration: A Preclinical Study.
Comparing the Independent Effects of Weight Loss or Exercise Training on Skeletal Muscle Lipid Localization and Insulin Sensitivity in Humans.

J Nutr. 2026 Aug 17. pii: S0022-3166(26)00438-4. [Epub ahead of print] 101789

Ingestion of 20 g of a plant-derived protein blend with and without added leucine or whey protein does not increase muscle protein synthesis rates in older males.

Lisa M E Kuin, Wesley J H Hermans, Noortje Boot, Cas J Fuchs, Joan M Senden, Antoine H Zorenc, Alexander Overman, Janneau M X van Kranenburg, Joy P B Goessens, Lex B Verdijk, Miriam van Dijk, Matthew Furber, Ardy van Helvoort, Luc J C van Loon.

   BACKGROUND: Sufficient high-quality protein intake is required to prevent sarcopenia in older adults. Plant-based proteins have been reported to have lesser anabolic properties when compared to animal-based proteins. Whether the lower quality of plant-based protein can be improved, thereby resulting in an anabolic response non-inferior to an equivalent amount of animal-based protein, remains to be established in older adults.
OBJECTIVE: To compare post-prandial muscle protein synthesis rates following ingestion of a single bolus of a soy-pea protein blend, with a soy-pea protein blend fortified with free leucine, or whey protein in older males.
METHODS: In this randomized, double-blind, parallel-group design, 45 healthy older males (aged 69±5 y, BMI 26.2±3.2 kg∙m-2) were selected to ingest a 20g protein blend combining 12g soy plus 8g pea protein (PLANT), 20g of the soy-pea protein blend fortified with 2g leucine (PLANT+LEU), or 20g whey protein (WHEY). Primed continuous L-[ring-13C6]-phenylalanine infusions were applied, with blood and muscle sampling up to 4 h after protein ingestion to assess plasma amino acid profiles and muscle protein synthesis rates.
RESULTS: WHEY increased plasma essential amino acid concentrations more than PLANT and PLANT+LEU over the 4 h post-prandial period (iAUC:135±20 vs 99±21 vs 105±21 mmol∙240 min∙L-1, respectively; P<0.001). Plasma peak leucine concentrations were higher following PLANT+LEU ingestion compared to PLANT and WHEY (567±74 vs 310±49 vs 471±74 μmol∙L-1, respectively; P<0.001). Post-prandial muscle protein synthesis rates averaged 0.034±0.010, 0.035±0.012, and 0.034±0.010 %∙h-1 following PLANT, PLANT+LEU, and WHEY ingestion, respectively (treatment P=0.828), and were not increased when compared to post-absorptive values.
CONCLUSION: Ingestion of 20 g protein alone, independent of its quality, is not enough to increase muscle protein synthesis rates in older males. More work is needed to define the preferred combination of both protein quality and quantity to stimulate muscle protein synthesis in an older population.
CLINICAL TRIAL REGISTRY NUMBER: NCT05711095 (clinicaltrials.gov).

Keywords:  aging; anabolic resistance; fractional synthetic rate; plant protein; stable isotopes

DOI:  https://doi.org/10.1016/j.tjnut.2026.101789
Aging Cell. 2026 Sep;25(9): e70678

Aged Mitochondrial DNA Is Associated With Aberrant Acute Exercise-Induced Redox Responses in Human Skeletal Muscle.

Bradley A Ruple, Nicholas A Carlini, Jason S Kofoed, Helya Rostamkhani, Brady E Hanson, Jesse C Craig, Shelby C Osburn, Allison M Manuel, Paul A Stewart, Jonathan Wanagat, Ryan M Broxterman, Joel D Trinity.

  Redox imbalances and mitochondrial dysfunction are key contributors to age-related declines in skeletal muscle and may contribute to impaired exercise responsiveness. Here, we investigated the influence of aging on skeletal muscle redox at rest and in response to acute exercise, examining how mitochondrial quality and quantity relate to skeletal muscle redox status. Skeletal muscle biopsies were obtained from 12 young (22 ± 4 years) and 10 older adults (66 ± 7 years) before and immediately after 60-min of high-intensity knee-extension exercise. We assessed mitochondrial respiration, mitochondrial DNA (mtDNA) copy number and deletion mutation frequency at baseline, while skeletal muscle redox proteomics was performed on pre- and post-exercise biopsies in a subset of participants. Mitochondrial respiration was preserved with age (max respiration, p = 0.123). However, the older adults had a lower mtDNA copy number (p = 0.046) and higher mtDNA deletion frequency (p = 0.001), with widespread remodeling of the skeletal muscle redox proteome, including altered thiol occupancy of proteins involved in metabolism, immune function, and extracellular matrix organization. In response to exercise, young skeletal muscle exhibited predominantly reversible peptide reductions, whereas preferential oxidation of mitochondrial antioxidant proteins, including PRDX3, occurred in older muscle. Both mtDNA deletion frequency and mitochondrial respiration were strongly associated with exercise-induced redox modifications in mitochondrial proteins. These findings suggest that aging alters both the regulation and resolution of exercise-induced redox signaling, with mitochondrial genomic instability and respiration shaping redox responsiveness.

Keywords:  aging; exercise; mitochondrial DNA; oxidative stress; redox proteomics

DOI:  https://doi.org/10.1111/acel.70678
Stem Cell Reports. 2026 Aug 20. pii: S2213-6711(26)00261-4. [Epub ahead of print] 103050

TDP-43 sustains satellite cells to maintain and regenerate skeletal muscle.

Theodore E Ewachiw, Tenaya K Vallery, Shloka Dhar, Hayden Clarkson, Tiffany Elston, Haileigh Gay, Bradley B Olwin.

  Skeletal muscle satellite cells (SCs), residing between the myofiber plasma membrane and the surrounding basement membrane, continue to maintain and repair skeletal muscle throughout life. Typically, quiescent SCs can transition into a reversible alert state (GAlert) that primes them for rapid activation to maintain or repair muscle. From GAlert, SCs can either re-enter quiescence or commit to the cell cycle, expand, and differentiate to fuse with existing regenerating myofibers. Exit from quiescence requires extensive post-transcriptional remodeling, including changes in RNA processing and RNA-binding protein activity. We show that TDP-43, an RNA-binding protein, is essential for SC maintenance and muscle repair. Conditional deletion of TDP-43 in SCs caused a consistent and progressive loss of GAlert SCs, even in uninjured muscle, leading to depletion of the SC pool. TDP-43 haploinsufficiency was sufficient to impair SC maintenance, indicating that both alleles are required. Integrative analysis suggests that TDP-43 supports the expression of stress response-associated transcripts during the quiescent-to- GAlert transition and that failure to mount this response contributes to SC apoptosis. Thus, we identified TDP-43 as a critical regulator of survival of SCs as these cells activate, and we establish that TDP-43 is required for the maintenance and repair of skeletal muscle.

Keywords:  RNP; TDP-43; muscle; muscle stem cell; myo-granule; regeneration; satellite cell

DOI:  https://doi.org/10.1016/j.stemcr.2026.103050
Eur J Appl Physiol. 2026 Aug 17.

Analytical approaches to account for muscle size when evaluating strength.

Matthew A Chatlaong, John P Bentley, Kealey J Wohlgemuth, Scott J Dankel, Jeremy P Loenneke, Matthew B Jessee.

  Skeletal muscle strength is multifactorial. Although associated, skeletal muscle size and strength often change disproportionately following resistance training with different loading paradigms. Examining strength relative to muscle size has been used to evaluate the potential contribution of muscle growth or other factors (e.g., neural or intramuscular adaptations) that occur with strength changes. Moreover, as muscle size could explain differing strength between individuals, comparisons of strength per unit of muscle size are sometimes used to account for differences in strength related to size. Several analytical approaches can be used to account for or hold muscle size fixed when evaluating strength. Based on prior work in sports medicine and other fields, we explored the use of ratio normalization and multiple regression techniques. Data from NHANES (1999-2002) and a previous investigation from our group were used in analysis demonstrations. In synthesizing and applying recommendations from previous work, we highlight some nuances and complexities with ratio normalization that may not be readily apparent without testing assumptions.

Keywords:  Hypertrophy; Muscle quality; Normalization; Resistance training; Specific force; Specific tension

DOI:  https://doi.org/10.1007/s00421-026-06376-6
Exp Physiol. 2026 Aug 19.

An acute crossover trial of passive movement training with and without blood flow restriction to determine the impact on postprandial glycaemia.

Jay Railton-Sowerby, Ewan Dean, Matthew Davitt, Jack Hayden, Ash Osborne, Donna Shrestha, David Cheneler, Christopher J Gaffney, Paul Hendrickse.

  During glucose uptake into muscle, GLUT-4 can translocate with stimulus from insulin or muscle contraction via exercise, but some exercise-intolerant populations are unable to benefit from improved glycaemic control. We investigated how passive movement training (PMT) and passive movement training with blood flow restriction (PMT+BFR) could be used as an alternative method. The effects on blood lactate and insulin were also investigated. Eleven healthy males (26.9 ± 8.3 years, 25.7 ± 2.1 kg/m2) undertook a crossover trial of three 150-min treatments, control (CTRL), PMT and PMT+BFR, on three separate study visits, separated by ≥24 h. Each participant arrived fasted and consumed a standardised high-carbohydrate meal (522 kcal, 112.5 g carbohydrate). The PMT protocol involved 30 min of intermittent bilateral knee extension/flexion (1 min:1 min work/rest) at an angular velocity of 180°/s through an 80° range of motion. PMT+BFR used a pressure calibrated at 80% arterial occlusion. Blood glucose and lactate were measured every 5 min, with insulin at 0, 30 and 60 min. Acute changes in muscle thickness were recorded using ultrasound pre- and post-intervention. There were no significant differences between the treatment groups for mean glucose (CTRL: 4.59 ± 0.48, PMT: 4.88 ± 0.82, PMT+BFR: 4.51 ± 0.90 mmol/L; P = 0.498). A statistically significant acute difference of muscle thickness (P = 0.00420) from pre- to post-treatment was detected in PMT+BFR. While PMT did not improve postprandial glycaemia with or without BFR, the acute increase in muscle thickness after PMT+BFR suggests that it may be useful in other applications.

Keywords:  BFR; blood flow restriction; exercise; glucose; glycaemic control

DOI:  https://doi.org/10.1113/EP093866
FASEB J. 2026 Aug 31. 40(16): e72197

Targeting TGF-β to Attenuate Ischemia-Reperfusion Associated Muscle Fibrosis and Enhance Regeneration: A Preclinical Study.

Hongru Ma, Zhenjia Zhong, Heng Zheng, Yutong Dai, Kaiyang Wang, Benlong Shi, Xu Sun, Zhen Liu, Yong Qiu, Zezhang Zhu, Fengfeng Li.

  Ischemia-reperfusion (IR) injury induces a pro-inflammatory cascade that disrupts inflammation resolution and exacerbates skeletal muscle fibrosis, leading to impaired regeneration through fibrosis and compromised myofiber regeneration. This study aimed to: (1) Demonstrate IR-induced dysregulation of muscle regeneration following acute injury; (2) Elucidating how TGF-β1 signaling within the FAP-associated inflammatory niche mediates fibrosis and impairs myofiber repair; and (3) Evaluating anti-TGF-β neutralization as a mechanism-based strategy to preserve regenerative capacity. Male C57BL6 mice (8 weeks) received CTX injections into the tibialis anterior (TA) to induce skeletal muscle injury. Transient clamping of femoral artery and vein was induced at 3 days post-injury to induce IR. Mice were stratified into CTX group and CTX-IR group depending on the induction of IR injury. TGF-β neutralizing antibody (TGF-β NAb) was administered in vivo to evaluate therapeutic potential. HE and Sirius red staining was used to assess cross-sectional area (CSA) of myofibers and percentage of fibrotic tissue. Western blotting was used to assess the expression of Collagen I, Collagen III and TGF-β. Flow cytometry was used to assess the number of fibro-adipogenic progenitors (FAPs). Collagen I and CD90 were assessed using immunostaining of TA cryosections and FAPs isolated from muscle tissues. The result shows that CTX-IR mice showed smaller myofiber cross-sectional area and more fibrotic tissue than CTX mice. Western blots revealed higher levels of Collagen I, Collagen III and TGF-β1 in CTX-IR samples. TGF-β1 stimulated the expression of collagen I in FAPs. TGF-β NAb application ameliorated the fibrosis of skeletal muscle and improved myofiber regeneration after IR. In conclusion, IR impairs muscle regeneration through TGF-β-associated FAP activation and collagen deposition. Inhibition of TGF-β attenuates fibrosis and increases the CSA of myofibers, demonstrating it as a potential target for promoting structural recovery and regenerative architecture in co-existing muscle injuries during orthopedic trauma.

Keywords:  fibrosis; ischemia–reperfusion; regeneration; skeletal muscle injury

DOI:  https://doi.org/10.1096/fj.202601893R
Diabetes. 2026 Aug 18. pii: db260239. [Epub ahead of print]

Comparing the Independent Effects of Weight Loss or Exercise Training on Skeletal Muscle Lipid Localization and Insulin Sensitivity in Humans.

Simona Zarini, Karin Zemski Berry, Amanda Garfield, Emily Macias, Purevsuren Jambal, Sophia Bowen, Melanie G Cree, Janet K Snell-Bergeon, Chris Johnson, P Darrell Neufer, Ian Tamburini, Marcus Seldin, Bryan C Bergman.

ARTICLE HIGHLIGHTS: Subcellular accumulation of lipids is linked to insulin resistance, but changes in localization from weight loss or exercise training have not been thoroughly explored. We evaluated the independent effects of two insulin-sensitizing interventions, weight loss and exercise training, on lipid subcellular distribution in fractionated skeletal muscle, muscle mitochondrial function, and gene expression. Exercise training increased cytosolic storage of diacylglycerols and sphingolipids, and weight loss increased cytosolic sphingosine and decreased mitochondrial/endoplasmic reticulum triacylglycerol and diacylglycerol accumulation. Exercise training prevented the negative effects of mitochondrial lipids on mitochondrial function. Changes in specific subcellular lipid storage help explain muscle insulin sensitization following lifestyle interventions.

DOI: https://doi.org/10.2337/db26-0239