Acta Physiologica最新文献

{"title":"Signal Amplification in the HPT Axis-Evidence for Its Existence, Location, Significance, and Molecular Mechanisms.","authors":"Li Jing, Sarahna A Moyd, Qiang Zhang","doi":"10.1111/apha.70202","DOIUrl":"10.1111/apha.70202","url":null,"abstract":"<p><p>Thyroid hormones (THs) are under negative feedback regulation via the hypothalamic-pituitary-thyroid (HPT) axis. How this axis operates to keep the circulating THs within a narrow physiological range is not well understood quantitatively. Led by the design principle of robust homeostatic feedback control, here we review and synthesize the literature under a unifying theme of signal amplification in the HPT axis, providing evidence for its existence, location, functional significance, and potential molecular mechanisms. Drawing on human studies of the circulating TSH-T4 relationship, we assert that a signal amplifier exists in the brain, where the TH feedback signal is amplified to inhibit TRH and TSH. With mathematical models we illustrate that placing the signal amplifier of the HPT feedback loop in the brain, not in the thyroid, provides an evolutionary advantage, which minimizes the disruption of operating TH levels by possible perturbations. We review the molecular neuroendocrine literature to reveal how signal amplification (ultrasensitivity) is likely achieved mechanically in the hypothalamus and anterior pituitary. We identify multiple signaling pathways in the TRH neurons, β2-tanycytes, and thyrotropes that mediate the feedback action of THs, including transcriptional and posttranslational regulations of the synthesis, maturation, degradation, and release of TRH and TSH. Collectively, these multistep regulations amplify T3 signal, providing a high feedback loop gain for robust TH homeostatic control. The nature's design principle revealed here enhances our cross-scale understanding of the systems biology of the HPT axis as a dynamical control system, which can promote precision thyroid medicine and risk assessment of thyroid-disrupting chemicals.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 4","pages":"e70202"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12-16 November 2025, Antalya, Türkiye.","authors":"","doi":"10.1111/apha.70212","DOIUrl":"https://doi.org/10.1111/apha.70212","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 Suppl 736 ","pages":"e70212"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin-(1-7) Alleviates Isoproterenol-Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor.","authors":"Xiaomei Wang, Fei Guo, Xiaoqian Wang, Yu Guo, Siyao Fan, Lan Hong, Honghua Jin","doi":"10.1111/apha.70200","DOIUrl":"10.1111/apha.70200","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study is to determine whether Angiotensin-(1-7) [Ang-(1-7)] alleviates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis through coordinated Mas receptor (MasR) and angiotensin II type-2 receptor (AT₂R) signaling, and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>ISO-induced hypertrophy was established in mice and assessed by echocardiography, histology, and hypertrophic markers. H9c2 cardiomyocytes were exposed to ISO and treated separately with A-779 (MasR antagonist), PD123319 (AT₂R antagonist), and a combination of both receptor antagonists. Receptor interplay was examined using pharmacological blockade and co-immunoprecipitation. Autophagy and apoptosis were evaluated by transmission electron microscopy and TUNEL.</p><p><strong>Results: </strong>Ang-(1-7) attenuated ventricular dysfunction, myocardial enlargement, and upregulation of hypertrophic markers in mice with ISO-induced hypertrophy. Pharmacological inhibition with A-779 and PD123319 revealed that Ang-(1-7) actions require reciprocal regulation between MasR and AT₂R. Both receptors synergistically contributed to the anti-apoptotic effect, while the anti-autophagic response was mediated predominantly by MasR. Transmission electron microscopy and TUNEL staining confirmed that Ang-(1-7) treatment alleviated excessive autophagy and apoptosis in cardiomyocytes. Furthermore, experiments with dual receptor antagonists and co-immunoprecipitation showed an interaction between MasR and AT₂R, supporting their coordinated signaling role in cardiac protection.</p><p><strong>Conclusion: </strong>Ang-(1-7) ameliorates ISO-induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis via synergistic MasR-AT₂R signaling. Receptor crosstalk may represent a therapeutic entry point for pathological hypertrophy.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 4","pages":"e70200"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12-16 November 2025, Antalya, Türkiye.","authors":"","doi":"10.1111/apha.70211","DOIUrl":"https://doi.org/10.1111/apha.70211","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 Suppl 736 ","pages":"e70211"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12-16 November 2025, Antalya, Türkiye.","authors":"","doi":"10.1111/apha.70208","DOIUrl":"https://doi.org/10.1111/apha.70208","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 Suppl 736 ","pages":"e70208"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative Beta-Hydroxy-Beta-Methyl-Butyrate Supplementation Reduces Mitochondrial Dynamics Proteins and Preserves Hepatic Mitochondrial Function After Partial Hepatectomy in Mice","authors":"A. L. Vieira-da-Silva,&nbsp;M. V. Esteca,&nbsp;F. A. Silva,&nbsp;I. A. Divino,&nbsp;F. S. Carneiro,&nbsp;E. R. Ropelle,&nbsp;A. S. Torsoni,&nbsp;I. L. Baptista","doi":"10.1111/apha.70204","DOIUrl":"10.1111/apha.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The liver exhibits a remarkable regenerative capacity, enabling this organ to maintain homeostasis even after significant injury. However, hepatic regeneration requires sufficient energy to sustain cellular hypertrophy and proliferation, thus ensuring efficient tissue repair. Therefore, dietary modulation of pathways regulating mitochondrial quality may enhance liver regeneration. This study aimed to investigate the effects of preoperative beta-hydroxy-beta-methylbutyrate (HMB) supplementation on mitochondrial quality control pathways and its impact on the liver regeneration process in mice undergoing partial hepatectomy (PHx).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6J mice were supplemented with 600 mg/kg HMB via <i>gavage</i> for 10 days. On the 10th day, supplementation was discontinued, and the mice underwent a ⅔ liver resection. The subsequent 7 days have constituted the liver regeneration period. For a second injury induction, at the end of the 7th day of regeneration, acetaminophen (APAP) overdose was administered via <i>gavage</i>. We then analyzed several markers of mitochondrial quality and liver function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results indicate that preoperative HMB supplementation modulates cell cycle progression, preventing excessive hepatic mass accumulation. Additionally, HMB regulates mitochondrial dynamics by decreasing Parkin, Mfn2, and DRP1 protein levels while increasing the mitochondrial markers VDAC2 and Tom20. Following a second injury from an APAP overdose, the HMB-supplemented group demonstrated increased mtDNA content and enhanced mitochondrial capacity, both critical for effective tissue recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that preoperative HMB supplementation preserves hepatic mitochondrial capacity after PHx.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Dependent Effects of Angiotensin II and Calcineurin in the Vasculature of Mice","authors":"Alexander Nolze,&nbsp;Sindy Rabe,&nbsp;Stefanie Ruhs,&nbsp;Nicole Strätz,&nbsp;Katja Quarch,&nbsp;Conny Köhler,&nbsp;Claudia Grossmann","doi":"10.1111/apha.70213","DOIUrl":"10.1111/apha.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cardiovascular diseases display strong sex differences. Angiotensin II (AngII) is implicated in this process. The ubiquitously expressed enzymatic beta subunit of calcineurin (PPP3CB), a serine/threonine phosphatase, can mediate pathological effects of AngII in the heart. Our aim was to explore the role of calcineurin in sex-dependent AngII-mediated vascular changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used female and male mice with a global PPP3CB knockout that were treated with AngII for 4 weeks as an in vivo model. For validation experiments and investigation of signaling pathways, primary aortic vascular smooth muscle cells (aVSMCs) isolated from respective female and male WT mice were utilized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AngII-induced increase in blood pressure was less pronounced and not calcineurin-dependent in female compared to male mice with no changes in media thickness or lumen area. Wire and pressure myography showed an AngII-induced calcineurin-dependent endothelial dysfunction in males but not in females. In aVSMCs from female mice, AngII did not influence wound closure or cell proliferation as was detectable in aVSMCs of male mice. As an underlying mechanism for these sex differences in long-term AngII effects, RNA-seq data and IPA revealed differentially regulated genes and pathways, involving extracellular matrix components, calcineurin, <i>Ctgf</i>, <i>Egfr</i>, and <i>Tgfb1</i>. Downstream of <i>Egfr,</i> we identified sex-dependent activation of PKC signaling in male and ERK/MAPK signaling in female as mediators of <i>Ctgf</i> expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, the relevance of AngII-calcineurin signaling for pathophysiological effects in the vasculature differs between female and male mice, suggesting both sexes require customized prevention and treatment strategies for cardiovascular disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progranulin Regulates Protein Synthesis in Myocytes Through an Ephrin Type A Receptor 2-Dependent Pathway","authors":"Ka Chon Chan,&nbsp;Hiong-Ping Hii,&nbsp;Hsin-Yu Kuo,&nbsp;Chung-Teng Wang,&nbsp;Kai-Pi Cheng,&nbsp;Horng-Yih Ou,&nbsp;Hung-Tsung Wu","doi":"10.1111/apha.70182","DOIUrl":"10.1111/apha.70182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sarcopenia is associated with metabolic dysregulation, yet the molecular mediators remain poorly defined. This study aimed to identify relevant regulators of muscle mass and to elucidate the role and underlying mechanism of progranulin in skeletal muscle protein synthesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We combined transcriptomic profiling of muscles from high-fat diet-fed mice with human genetic data from the HugeAMP Type 2 Diabetes Knowledge Portal to identify potential regulators. Clinically, 172 participants were stratified into low muscle mass (LMM) and normal muscle mass (NMM) groups according to the Asian Working Group for Sarcopenia criteria, and serum progranulin was measured. In vitro, recombinant progranulin was applied to L6 myoblasts to assess proliferation and differentiation and to differentiated L6 myotubes to evaluate protein synthesis and mTOR/S6K/S6 signaling. We performed shRNA-mediated knockdown of Ephrin type-A receptor 2 (EphA2), a functional progranulin receptor, to determine its impact on progranulin-induced effects in L6 myotubes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transcriptomics identified <i>Grn</i> as a top downregulated gene in metabolically stressed muscle. Clinically, serum progranulin levels were significantly lower in the LMM group than the NMM group (280.71 ± 148.09 vs. 378.96 ± 139.65 ng/mL, <i>p</i> &lt; 0.001). In vitro, progranulin did not affect the proliferation or differentiation of L6 myoblasts. However, it dose-dependently enhanced protein synthesis and increased phosphorylation of mTOR, S6K, and S6 in L6 myotubes. Furthermore, EphA2 knockdown attenuated progranulin-induced protein synthesis and phosphorylation of mTOR, S6K, and S6.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Progranulin acts as a novel regulator of skeletal muscle metabolism, which enhances protein synthesis through EphA2-mediated activation of the mTOR signaling cascade.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of Sepsis, Disuse, and Aging on Skeletal Muscle Function and Remodeling in Male and Female Mice","authors":"Diana C. Muller,&nbsp;Franccesco P. Boeno,&nbsp;Gisienne Reis,&nbsp;Armina Azam,&nbsp;Malaica Ashley,&nbsp;Yumei Zhou,&nbsp;Feng Yue,&nbsp;Terence E. Ryan,&nbsp;Philip A. Efron,&nbsp;Orlando Laitano","doi":"10.1111/apha.70195","DOIUrl":"10.1111/apha.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis is associated with skeletal muscle weakness and atrophy, particularly in older and immobilized patients; however, how sepsis interacts with disuse, reloading, aging, and biological sex remains poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young (5 mo) and older (20 mo) male and female C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham surgery followed by hindlimb suspension (HLS) or normal ambulation (NA) for 7 days (Experiment 1). A separate cohort underwent 3 days of reloading after HLS (REL; Experiment 2). Outcomes included survival, body mass, soleus force–frequency, myofiber cross-sectional area (CSA), macrophage infiltration (CD68⁺), extracellular matrix (ECM), and satellite cells (Pax7⁺).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Survival was preserved in septic young mice (&gt; 84%) but reduced in older septic mice (~51%–60% males; ~57% females). Disuse was the primary driver of body mass loss during HLS/REL, with older females exhibiting the greatest decline (day 11: −19.8% ± 6.8% Sham; −17.4% ± 6.5% CLP). Disuse reduced median fiber CSA by ~27%–46% across cohorts (e.g., young males: 1840 ± 189 to 997 ± 345 μm²). In Experiment 1, CD68⁺ macrophages increased most with combined sepsis and disuse, whereas ECM expansion was observed only in males. Pax7⁺ satellite cells were markedly reduced in young males with sepsis and disuse and in older mice of both sexes with sepsis. Following REL, older septic males retained force deficits, and septic females remained significantly atrophic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Muscle disuse amplifies sepsis-induced myopathy in an age- and sex-dependent manner, with incomplete early recovery after reloading.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sepsis, Disuse, Aging, and Sex: A Toxic Quartet Crippling Muscle Recovery","authors":"Alexandra M. Winant,&nbsp;Julien Ochala","doi":"10.1111/apha.70203","DOIUrl":"10.1111/apha.70203","url":null,"abstract":"&lt;p&gt;Sepsis survivors face profound muscle weakness, which is often exacerbated by immobility in the intensive care unit (ICU), advanced age, and sex disparities; however preclinical models have historically overlooked these interacting factors. A recent landmark study in &lt;i&gt;Acta Physiologica&lt;/i&gt; by Muller and colleagues [&lt;span&gt;1&lt;/span&gt;] integrates cecal ligation and puncture (CLP)-induced sepsis with hindlimb suspension (HLS) in young (5 months) and older (20 months) male and female C57BL/6J mice, thereby recapitulating bedrest in septic patients and incorporating reloading to probe early recovery dynamics. Disuse emerges as the dominant driver of catastrophic atrophy (27%–46% reduction in median soleus fiber cross-sectional area, CSA) and absolute force deficits across all groups. In contrast, sepsis alone subtly impairs intrinsic contractile quality (specific force) most strikingly in females. Survival plummets to ~50%–60% in older septic mice versus &gt; 84% in young mice, while disuse exerts a negligible impact on mortality, spotlighting age as the primary vulnerability in sepsis.&lt;/p&gt;&lt;p&gt;Each year, sepsis affects nearly 50 million patients globally, many of whom experience muscle weakness that persists for months after hospital discharge, driving up readmissions and reducing quality of life [&lt;span&gt;2&lt;/span&gt;]. In this study, HLS mirrors the prolonged immobility common in septic shock, identifying disuse (rather than sepsis alone) as the main culprit for the dramatic muscle wasting and force loss. Body mass declines by 10%–21%, with the greatest losses observed in older females. Brief reloading after disuse fails to fully restore function: older males retain high-frequency force deficits, while females exhibit persistent fiber atrophy. These findings echo clinical trials of early mobilization, which demonstrate benefit in some patients, but reduced efficacy in the elderly or septic, signaling the need for tailored rehabilitation strategies [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Across all ages and conditions, disuse slashes absolute muscle force by 25%–50% at physiological stimulation frequencies, accompanied by similar reductions in fiber sizes (young males lose nearly half their CSA). When force is normalized to fiber size (specific force), however, a marked sex difference is revealed: females exhibit greater intrinsic contractile impairment, suggesting disruptions in calcium handling or myofilament interactions specific to their muscle physiology. In males, by contrast, weakness is more closely linked to loss of muscle mass. Clinically, these findings suggest that women may benefit from therapies that preserve muscle quality (such as agents that stabilize contraction machinery), while men may respond more to antiatrophy measures.&lt;/p&gt;&lt;p&gt;The synergy of sepsis and disuse increases macrophage infiltration up to eightfold, peaking in young females, and promotes collagen accumulation in the male muscle extracellular matrix—findings that mirror human intensive care ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}