American journal of physiology. Cell physiology最新文献

{"title":"Proteomic profile of urinary extracellular vesicles from rats with lithium-induced nephrogenic diabetes insipidus.","authors":"Camilla Grønkjær, Lei Cheng, Qi Wu, Xabier Sørtvedt, Luciano D'Apolito, Soham Rej, Robert A Fenton, Francesco Trepiccione, Birgitte M Christensen","doi":"10.1152/ajpcell.00182.2026","DOIUrl":"10.1152/ajpcell.00182.2026","url":null,"abstract":"<p><p>Lithium (Li) salts have been widely used to treat bipolar disorder and unipolar depression for more than 50 yr. However, up to 40% of people taking Li develop nephrogenic diabetes insipidus (NDI). NDI is associated with cellular remodeling in the rodent kidney collecting duct (CD) and reduced aquaporin-2. Patients taking Li for more than 10-20 yr are at risk of chronic kidney disease, which ultimately can lead to end-stage renal disease, hemodialysis, transplantation, or death. The purpose of this study was to investigate whether the rat urinary proteome can be used as an indicator of Li-induced changes in the kidney. Extracellular vesicles were isolated from the urine of rats treated with Li for 2 or 4 wk, followed by LC-MS/MS analysis. The results showed a limited correlation between protein changes in the urine and the kidney. However, the urine contained markers of mitochondrial dysfunction. The cytoskeletal protein, keratin 8, showed a tendency to be higher in the urine and was greatly increased in collecting duct principal cells in response to Li, suggesting a potential role in cellular remodeling. Canonical histone H4 was increased in the urine and was observed in the nuclei of collecting duct principal and intercalated cells following Li. Moreover, histone H4-positive cells colocalized with the proliferation marker, proliferating cell nuclear antigen (PCNA). This correlates with the known increased proliferation in the collecting duct in response to Li. Thus, replication-dependent histone H4 is a possible urinary marker for the Li-induced cellular remodeling of the collecting duct.<b>NEW & NOTEWORTHY</b> Lithium (Li) increases replication-dependent histone H4 in urine and in principal and intercalated cells, so histone H4 is a possible urinary marker for Li-induced cellular remodeling.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C485-C494"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence as a regulatory mechanism in skeletal muscle repair in young mice.","authors":"Amanda L Johnson, Ryan T Bevington, Gianni Parise","doi":"10.1152/ajpcell.00154.2026","DOIUrl":"10.1152/ajpcell.00154.2026","url":null,"abstract":"<p><p>Senescence is broadly considered an age-related phenomenon; however, it also been implicated in normal tissue repair and wound healing. Skeletal muscle repair is a complex process that requires the coordination of several different cell populations, but the role of senescence in skeletal muscle repair has yet to be fully elucidated. We hypothesize that senescence serves as a control mechanism throughout the regenerative process, and the removal of senescent cells through senolytics will negatively impact the repair process in young mice. Briefly, young mice were exposed to either <i>1</i>) vehicle (VEH), receiving only a cardiotoxin (CTx) injection in one hindlimb, or <i>2</i>) 7 days of senolytic treatment (SEN) pre-CTx and 3×/week for 4 wk post-CTx. Dasatinib + Quercetin (D + Q) was used to selectively eliminate senescent cells. There were no significant differences between groups in functional measures such as hindlimb grip strength and cross-sectional area. eMHC+ fibers remained elevated at D28 in the SEN group. Macrophage infiltration was twice as high in the SEN group compared with VEH at D7. Satellite cell quantity and fibrotic area were significantly increased at D14 in the SEN group compared with VEH. We conclude that reducing senescent cells during muscle repair in young mice significantly altered the kinetics of muscle repair. Therefore, senescent cells may act as a regulatory mechanism in skeletal muscle to orchestrate the activity of the different cell populations involved in repair and regeneration, such as immune cells, satellite cells, and fibrotic cells.<b>NEW & NOTEWORTHY</b> Senolytic treatment in young mice results in a transient delay in the repair kinetics of satellite cells, macrophages, and fibrosis without disrupting functional repair of skeletal muscle. Fibers associated with a p21+ nucleus were smaller in size than myofibers not associated with a p21+ nucleus, possibly signifying areas with delayed or incomplete repair or where greater senescence-associated signalling is needed to regulate nearby cell populations.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C316-C327"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle biomass as an underappreciated fate of glucose.","authors":"Henning Wackerhage, Moritz Eggelbusch, Juha J Hulmi, Sakari Mäntyselkä","doi":"10.1152/ajpcell.00295.2026","DOIUrl":"10.1152/ajpcell.00295.2026","url":null,"abstract":"<p><p>Glucose is traditionally viewed as a substrate for ATP production and glycogen storage in skeletal muscle. Here, we review evidence that glucose also serves as a building block for biomass synthesis in proliferating muscle satellite (stem) cells and hypertrophying skeletal muscle fibers, drawing parallels to anabolic metabolic reprogramming in cancer cells. In cancer and other growing cells, increased glucose uptake, aerobic glycolysis (Warburg effect), and the TCA cycle provide substrates for anabolic pathways that generate macromolecules required for growth and proliferation. Radiotracer studies in mammalian cancer and muscle cells demonstrate that approximately 8%-15% of the cell dry mass originates from glucose. Mechanistic insights, obtained predominantly from cell culture models, indicate that glucose-derived glycolytic and TCA cycle intermediates provide substrates for serine synthesis and the pentose phosphate pathway, glycine and one-carbon metabolism, nonessential amino acid synthesis, nucleotide and lipid synthesis, as well as for epigenetic methylation and acetylation. We further review evidence that human resistance training, hypertrophy through muscle-specific expression of <i>Akt1</i> in mice, loss or inhibition of myostatin/activin signaling, and other hypertrophy-inducing interventions improve glucose homeostasis under conditions of obesity, insulin resistance, and type 2 diabetes. We discuss the possibility that glucose incorporation into biomass contributes to this effect.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C405-C414"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pervasive negative regulation of ion channel functional families across human cancers.","authors":"Luca Visentin, Luca Munaron, Paola Cassoni, Luca Bertero, Alessia Andrea Ricci, Giorgia Chinigò, Federico Alessandro Ruffinatti","doi":"10.1152/ajpcell.00712.2025","DOIUrl":"10.1152/ajpcell.00712.2025","url":null,"abstract":"<p><p>The transmembrane transport of molecules and ions is fundamental to cellular homeostasis and coordination of physiological processes. During tumorigenesis, these processes undergo significant alterations in response to oncogenic transformations and microenvironmental pressures. However, a comprehensive systems-level characterization of transportome alterations across cancer types has been lacking. Here, we integrate structural, functional, and mechanistic annotations of all known human ion channels and transporters (ICTs) into a curated database, organizing them into biologically coherent gene sets based on shared physiological and biophysical properties such as permeant species, gating mechanism, and transport directionality. By leveraging Gene Set Enrichment Analysis across transcriptomic profiles from 19 tumor types, we reveal a recurrent downregulation of multiple ICT families-particularly ion channels-accompanied by selective upregulation of specific pump classes. Paired Clinical Proteomic Tumor Analysis Consortium transcriptomic-proteomic datasets further support this signature, showing that transportome tumor-normal transcript changes are largely preserved at the protein level, with high directional concordance. We interpret this pattern as a molecular signature of cancer-associated dedifferentiation and sensory signal decoupling, pointing toward a broader and underappreciated strategy by which tumors reconfigure their transmembrane communication interfaces to favor autonomy, immune evasion, and metabolic adaptation. Our findings uncover a widely conserved transportome reprogramming and provide a quantitative framework for future integrative studies of ICT function and their roles in cancer systems biology.<b>NEW & NOTEWORTHY</b> We provide a novel computational framework for transportome analysis. By applying it to transcriptomics and proteomics large public datasets, we found a striking and previously unrecognized pattern whereby ion channel families are consistently downregulated, whereas most transporter families are either preserved or upregulated. This functional asymmetry suggests a widespread suppression of channel-mediated signaling processes as a general strategy by which tumors reconfigure their transmembrane communication interfaces to favor dedifferentiation, autonomy, immune evasion, and metabolic adaptation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C458-C484"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial expression of myocardin protein in normal and disease states.","authors":"Jaser Doja, Nestor Ishimwe, Amr R Salem, Orazio J Slivano, Wei Zhang, Ajay Kumar, Xiaochun Long, Joseph M Miano","doi":"10.1152/ajpcell.00061.2026","DOIUrl":"10.1152/ajpcell.00061.2026","url":null,"abstract":"<p><p>Vascular smooth muscle cell (VSMC) dedifferentiation, a phenomenon found in virtually all vascular diseases, is characterized by a transcriptional switch from a contractile to a phenotypically modulated state. Myocardin (MYOCD) is a smooth muscle cell-restricted coactivator that is necessary and sufficient for the differentiation of VSMC through the transcriptional activation of SMC-restricted cytoskeletal and contractile genes. Despite 25 yr of research on MYOCD, the reliable expression of this protein continues to be poorly represented and understood. Accordingly, we generated a novel rat model carrying HA-tagged MYOCD to address pervasive disparities in the literature and elucidate MYOCD protein expression in vivo. Western blotting studies documented the highest MYOCD protein expression in aorta, bladder, and uterus, with low or undetectable expression in all other tissues of the rat, including heart. Predictive modeling supports the C-terminus of MYOCD to be most immunoreactive, where the HA tag and one other commercial immunogen reside. Of note, the latter immunogen was used to generate what appears to be the most trustworthy commercial antibody against MYOCD. In vitro transcription/translation and phosphatase treatment of ectopic and endogenous MYOCD protein reveal an intrinsically high molecular weight of MYOCD that has eluded prior reports. Importantly, we present the very first spatial expression profile of MYOCD protein in several mouse and rat tissues under baseline and vascular injury conditions. The results offer the SMC community new resources and insight into the reliable detection of MYOCD protein.<b>NEW & NOTEWORTHY</b> Endogenous MYOCD protein has eluded reliable detection due to pervasive commercial antibody failures, likely due to protein disorder. A CRISPR-generated 3xHA knock-in rat enabled the first in vivo spatial characterization of MYOCD, revealing its presence in SMC-rich tissues and, notably, within the microvasculature of SMC-poor organs. Phosphorylation largely accounts for the high molecular weight of MYOCD. Strikingly, MYOCD is detected in neointimal cells after vascular insult, suggesting persistence or reexpression during vascular remodeling.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C301-C315"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nonhydrolyzable candesartan cilexetil analog reveals synergistic activation as a tractable mechanism for TMEM175 modulation.","authors":"Kangjun Li, Samantha D Le, Vaishali Satpute Janve, Roman M Lazarenko, Ian M Romaine, Kwangho Kim, Gary A Sulikowski, Alex G Waterson, Jerod S Denton","doi":"10.1152/ajpcell.00348.2026","DOIUrl":"10.1152/ajpcell.00348.2026","url":null,"abstract":"<p><p>TMEM175 is a lysosomal cation channel essential for maintaining lysosomal pH and function. Dysregulation of TMEM175 has been implicated in Parkinson's disease, highlighting the need for small-molecule modulators to probe its physiological and therapeutic roles. We previously screened an FDA-approved compound library for TMEM175 modulators using a plasma membrane overexpression system that enables functional analysis of channel activity. Here, we report the pharmacological characterization of the most potent hit, candesartan cilexetil. In fluorescence-based thallium flux, automated patch-clamp, and manual patch-clamp assays, candesartan cilexetil robustly activates TMEM175 with efficacy comparable with the reference activator DCPIB, whereas its hydrolyzed metabolite candesartan is inactive. Candesartan cilexetil is active only when applied to the extracellular (lysosome lumen-equivalent) side of the channel and is inactive from the cytosolic-facing side. To determine whether activation requires the intact prodrug, we generated analogs that modify or eliminate the cilexetil and ester functionalities. Structure-activity studies show that selected modifications of the cilexetil moiety reduce potency while preserving maximal efficacy, whereas more extensive modification markedly reduces intrinsic activity, indicating that it is an essential pharmacophoric element rather than a simple membrane-permeating handle. Manual patch-clamp wash-off experiments further demonstrate direct, reversible activation without requiring membrane permeation or hydrolysis. Unexpectedly, the nonhydrolyzable analog VU0982645 exhibits minimal intrinsic activity yet produces robust synergistic activation with DCPIB. Together, these findings establish the cilexetil handle as a key pharmacophoric element and support synergistic modulation as a tractable mechanism for activating TMEM175.<b>NEW & NOTEWORTHY</b> We introduce a new therapeutic paradigm for TMEM175 targeting by demonstrating that synergistic agonist pairs can drive robust channel activation. Beyond identifying candesartan cilexetil as a moderately potent activator with a previously unrecognized pharmacophoric cilexetil moiety, we show that a minimally active analog can dramatically potentiate activation in combination with DCPIB. This synergistic strategy establishes TMEM175 as a tractable therapeutic target and reveals coagonism as a powerful mechanism to modulate lysosomal ion channels.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C415-C424"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-339-5p impairs myogenic proliferation and differentiation by repressing contractile gene programs in skeletal muscle.","authors":"Xue Yu, Elena Caria, Dimitrius Santiago P S F Guimarães, Maxence Jollet, David Rizo-Roca, Alesandra A Marica, Souren Mkrtchian, Marta Gómez-Galán, Anna Krook, Nicolas J Pillon","doi":"10.1152/ajpcell.00898.2025","DOIUrl":"10.1152/ajpcell.00898.2025","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are critical regulators of skeletal muscle development and adaptation, orchestrating the balance between proliferation, differentiation, and tissue repair. Here, we identify miR-339-5p as a previously unrecognized, conserved regulator of skeletal muscle remodeling. Transcriptomic analysis from human, mouse, and rat studies revealed that miR-339-5p is consistently upregulated in skeletal muscle under conditions of stress or injury and declines during myogenic differentiation in vitro. Gain-of-function experiments demonstrated that miR-339-5p overexpression impairs expression of genes associated with myogenic differentiation and promotes expression of proliferative markers in both primary human myotubes and mouse C2C12 cells. Transcriptomic profiling confirmed widespread repression of pathways involved in cytoskeletal organization, myofibrillar assembly, and mitochondrial function. In vivo, electroporation-mediated overexpression of miR-339-5p in mouse tibialis anterior altered regeneration-associated gene expression and increased the number of immature fibers, therefore modulating tissue remodeling during postinjury growth. Integrated analyses combining target prediction algorithms, differentiation-associated correlations, and overexpression datasets identified seven conserved high-confidence miR-339-5p targets, among which the autophagy-associated phosphatase myotubularin related protein 3 (<i>MTMR3</i>) emerged as the most consistently regulated candidate. Collectively, our data demonstrate that miR-339-5p functions as a conserved inhibitor of myogenic progression, linking injury-induced stress responses to delayed differentiation and altered muscle remodeling. These findings establish miR-339-5p as a potential therapeutic target in conditions characterized by impaired muscle regeneration or dysregulated tissue remodeling.<b>NEW & NOTEWORTHY</b> We uncover miR-339-5p as a conserved microRNA that suppresses myogenic proliferation and differentiation and reshapes contractile gene networks in skeletal muscle. Its induction after injury and ability to alter regeneration and fiber morphology in vivo highlight miR-339-5p as a regulator of muscle repair or remodeling.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C425-C440"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxaloacetate inhibition of succinate dehydrogenase: mechanism and physiological implications.","authors":"William I Sivitz, Liping Yu","doi":"10.1152/ajpcell.00200.2026","DOIUrl":"10.1152/ajpcell.00200.2026","url":null,"abstract":"<p><p>As has been known for many decades, oxaloacetate (OAA) is a very potent inhibitor of succinate dehydrogenase (SDH). However, the phenomenon has received little attention for several reasons to be discussed. Although the interaction between OAA and the structure of SDH has been scrutinized, there has been little attention to the mechanism underlying OAA inhibition of SDH in respiring mitochondria or to its functional implications. In recent years, we have used more advanced methodology to examine these issues. OAA is unstable and therefore very difficult to detect by mass spectroscopy. Hence, we used a novel NMR approach to assess OAA in mitochondria of muscle, brown adipose tissue, and liver under active respiratory conditions. We also used a modification of existing technology to assess mitochondrial respiration in states apart from the extremes of <i>state 4</i> and <i>state 3</i>. We found strong evidence that mitochondrial OAA content and inhibition of SDH are dependent on inner mitochondrial membrane potential (ΔΨ) and the effects of ΔΨ on the NADH/NAD⁺ redox state. Furthermore, we examined the effects of perturbed OAA content by deleting glutamic-oxaloacetic transaminase, which metabolizes OAA and glutamate to aspartate and α-ketoglutarate. Such deletion enhanced mitochondrial OAA and impaired metabolism through SDH. Here, we review historical and recent studies addressing OAA inhibition of SDH. We also discuss the possible physiological role of OAA/SDH interaction and whole-body consequences. Furthermore, we describe a novel methodology for the detection of OAA and assessment of mitochondrial function under conditions of clamped mitochondrial inner membrane potential.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C393-C404"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat, low-carb diet reduces tumor growth and induces liver metabolism remodeling in a breast cancer mouse model.","authors":"Anouk Charlot, Anthony Bringolf, Joris Mallard, Amélie Jaulin, Emilie Crouchet, Delphine Duteil, Fabien Alpy, Catherine-Laure Tomasetto, Thomas F Baumert, Joffrey Zoll","doi":"10.1152/ajpcell.00878.2025","DOIUrl":"10.1152/ajpcell.00878.2025","url":null,"abstract":"<p><p>Cancer cells require large quantities of glucose to ensure sufficient ATP production through glycolysis, and the liver may facilitate this glucose supply. A high-fat low-carbohydrate ketogenic diet (KD) could represent a strategy to reduce tumor growth. However, the molecular effects of carbohydrate restriction mediated by the KD and its hepatic impact remain poorly understood. To address this question, 6-wk-old FVB/N-Tg(MMTV-PyVT)634Mul/J mice, which develop spontaneous mammary tumors, were fed a standard chow diet (SD group) or a KD diet (KD group) until reaching the age of 12 wk. The effects of carbohydrate restriction were assessed by plasma analyses, as well as histological staining, RT-qPCR, and Western blotting in tumors and liver. We found that carbohydrate restriction reduced tumor growth by 46% and was associated with decreased expression of protumorigenic factors (<i>Ang2</i>, <i>Hgf</i>, and <i>Mki67</i>). Moreover, a decrease of metabolic enzymes (<i>Pfk</i>, <i>Bdh1</i>, and <i>Scot1</i>) highlighted the lack of metabolic flexibility of the tumor cells and underscored their strong dependency on glucose. Conversely, the liver exhibited a strong adaptive response with enhanced ketogenesis and gluconeogenesis, evidenced by elevated blood glucose and upregulation of <i>Pepck</i>, <i>Foxo1</i>, and CREB. A high-fat, low-carbohydrate diet exerts a dual metabolic effect: it suppresses tumor progression through local metabolic reprogramming but simultaneously enhances hepatic glucose production. This highlights the pivotal role of systemic glucose availability in tumorigenesis and underscores the need to consider liver metabolism when designing dietary interventions for cancer therapy.<b>NEW & NOTEWORTHY</b> We demonstrate that carbohydrate restriction alone slows breast tumor growth by limiting glucose availability and exposing the metabolic inflexibility of cancer cells. Despite an antitumor effect, carbohydrate restriction also triggers a robust hepatic compensatory response that increases endogenous glucose production. These findings provide important new insights for the design of metabolic interventions in oncology, highlighting the central role of liver-tumor metabolic cross talk and showing that dietary strategies should consider whole body glucose homeostasis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C237-C251"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle satellite cells and aging.","authors":"Amanda L Johnson, Ryan T Bevington, Samuel Rumelski, Natasha Kassamali, Gianni Parise","doi":"10.1152/ajpcell.00232.2026","DOIUrl":"10.1152/ajpcell.00232.2026","url":null,"abstract":"<p><p>Aging is associated with a progressive decline in skeletal muscle mass and function, contributing to reduced physical capacity in older adults. Central is the deterioration of satellite cells, our tissue-resident muscle stem cells, which participate in adaptation, repair, and regeneration of skeletal muscle. Evidence from in vitro, murine, and human studies indicates an age-related reduction in satellite cell content, notably within type II muscle fibers, alongside impairments in myogenic potential. There is no single causative mechanism behind satellite cell age-related dysfunction, but a convergence of morphological changes and intrinsic and extrinsic factors that affect satellite cell dynamics and its niche. Intrinsic factors such as signaling pathways, cellular senescence, impaired autophagy, mitochondrial dysfunction, and epigenetic modifications can impact satellite cell function. Concurrently, extrinsic factors can impact the satellite cell niche and their function such as systemic circulating factors and vasculature and extracellular matrix remodeling. These age-related alterations can diminish regenerative capacity, blunt hypertrophic responses, and impair recovery from disuse or injury. Satellite cell dysfunction is a pivotal contributor to age-related skeletal muscle decline, frailty, and the quality of life in older adults. Despite growing insights from in vitro and animal models, the key mechanistic changes that underlie human satellite cell dysfunction with age are not fully understood. Improved characterization of age-related satellite cell changes in humans is essential to preserving muscle health across the lifespan.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C497-C511"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}