Physiological genomics最新文献

{"title":"Prepartum E2-driven tissue-specific transcriptomic changes in the ewe reproductive tract.","authors":"Bethania J Davila Ruiz, Chutikun Kanjanaruch, Wellison J S Diniz, Priyanka Banerjee, Carl R Dahlen, Pawel P Borowicz, Christopher S Schauer, Mara R Hirchert, Joel S Caton, Alan J Conley, Lawrence P Reynolds","doi":"10.1152/physiolgenomics.00296.2025","DOIUrl":"10.1152/physiolgenomics.00296.2025","url":null,"abstract":"<p><p>Estrogens regulate key processes in parturition, yet the specific effects of estradiol (E2) on maternal reproductive tissues in sheep remain unclear. This study investigated the impact of exogenous E2, mimicking physiological prepartum levels, on gene expression in the myometrium, endometrium, cervix, and placental membranes, as well as sex steroid receptor protein expression in uterine compartments of late pregnant ewes. Pregnant ewes (139-142 days gestation) received Silastic implants containing either E2 (200 µg/ewe, <i>n</i> = 6) or control (<i>n</i> = 6), and tissues were collected 26 h post-treatment. Bulk RNA sequencing assessed differential gene expression, while fluorescence immunohistochemistry evaluated nuclear receptor localization and intensity. Transcriptomic analysis (FDR < 0.05) revealed a tissue-specific response, with the cervix showing the most robust transcriptional changes. Gene Ontology enrichment indicated downregulation of extracellular matrix organization pathways associated with cervical dilation at parturition. Targeted analyses revealed regulation of genes related to prostaglandin synthesis, steroid metabolism, immune signaling, and ECM remodeling. The endometrium displayed a moderate response, whereas the myometrium and placental tissues exhibited minimal changes. At the protein level, myometrial progesterone receptor (PR) expression was significantly reduced (<i>P</i> < 0.05), while ERα and ERβ were unaffected. These findings demonstrate that the prepartum rise in E2 is associated with tissue-specific gene expression changes in the ewe uterine tract. In the cervix, the most affected tissue, transcriptomic changes are consistent with cervical ripening. Reduced myometrial PR expression suggests decreased progesterone responsiveness.<b>NEW & NOTEWORTHY</b> Exogenous estradiol treatment in late-gestation ewes induced distinct, tissue-specific transcriptomic changes, with the cervix showing the most pronounced response. In addition, estradiol was associated with reduced progesterone receptor protein expression in the myometrium. Together, these findings suggest that estradiol may play a role in coordinating prepartum changes in reproductive tissues in ewes, consistent with its known actions near term in other species.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"577-588"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial serine protease EspP induces differentiation and expansion of enteroendocrine cells in human colonoids.","authors":"Myranda N Thompson, Ruixuan Liu, Cristina N Coffman, Allison M Kilpatrick, Lito L Appell, Roger Atanga, Julie G In","doi":"10.1152/physiolgenomics.00094.2026","DOIUrl":"10.1152/physiolgenomics.00094.2026","url":null,"abstract":"<p><p>Extracellular serine protease, plasmid-encoded (EspP) is a potent serine protease that functions as a cytotoxin and is secreted by enterohemorrhagic <i>Escherichia coli</i> (EHEC). This bacterial toxin can cause significant colonic epithelial damage and mimic the pathophysiology of EHEC infection on human colonic organoids. However, transcriptomic changes within the intestinal epithelial cells and impacts on cell proliferation and differentiation are largely unknown. Here, using human colonic organoids, we defined the molecular and cellular changes that occur in response to acute EspP exposure, independent of microbiota, stroma, and immune cells. We performed droplet-based single-cell RNA sequencing to determine changes in epithelial cell lineages in response to EspP and demonstrated that there is a disruption in proliferation and a preferential differentiation of enteroendocrine cells (EECs). Higher-resolution clustering revealed that the de novo EECs were primarily enterochromaffin or EEC progenitors. Interestingly, EECs induced from EspP treatment displayed an immune profile, expressing cytokines and chemokines associated with macrophage or neutrophil recruitment. These findings demonstrate that EspP, a potent EHEC cytotoxin, stimulates transcriptomic changes previously attributed to the whole bug infection and highlights the significance of crypts-based proliferative cells and secretory cell differentiation as major colonic responses to bacterial pathogens.<b>NEW & NOTEWORTHY</b> EspP, a bacterial serine protease secreted by enterohemorrhagic <i>E. coli,</i> can mimic the intestinal pathophysiology of EHEC in the absence of the bacteria. Using single-cell RNA sequencing, this study identified enteroendocrine cells as early responders to EspP treatment, with preferential hyperplasia of enterochromaffin cells. EspP-induced enteroendocrine cells also expressed immune cytokines and chemokines. This highlights the importance of enteroendocrine cell responses to bacterial pathogens and intestinal pathophysiology during infection.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"552-564"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonistic effects of hypersalinity on heat tolerance in a copepod emerge from nonadditive protein abundance changes.","authors":"Caroline E Terry, Maxime Leprêtre, Dietmar Kültz, W Wesley Dowd","doi":"10.1152/physiolgenomics.00005.2026","DOIUrl":"10.1152/physiolgenomics.00005.2026","url":null,"abstract":"<p><p>Nonadditive interactions between environmental stressors, where biological responses to simultaneous stressors do not equal the sum of individual-stressor responses, commonly occur across organisms and environments. To enable predictions of organismal resilience to shifting patterns of environmental stressors, it is important to both identify these interactions and document the mechanisms underlying them. The supratidal copepod <i>Tigriopus californicus</i> demonstrates a nonadditive, antagonistic pattern of increased heat tolerance when simultaneously exposed to high salinities. We investigated salinity's chronic and acute effects on heat tolerance in a northern population and quantified responses in protein abundance to hypersalinity and heat stress, both alone and in combination. The overall proteomic response to multiple stressors was nonadditive and largely reflected that to high temperature. However, 42% of multistressor proteins were absent from either single-stressor response; we refer to these proteins that are only differentially abundant in the multistressor scenario as \"emergent.\" Our results suggest that the increased heat tolerance of <i>T. californicus</i> conferred by hypersalinity may be driven by a combination of these emergent proteins, several proteins induced by hypersalinity in both single- and multistressor conditions that may contribute to cross-tolerance, and four proteins with additive abundance patterns (including a small heat shock protein). These candidate proteins play putative roles in several relevant processes including the heat shock response, protein folding, and regulation of metabolism and oxidative stress responses. Our results connect to prior whole organism findings and highlight promising pathways for future investigation in the context of heat tolerance and multistressor interactions.<b>NEW & NOTEWORTHY</b> Protein abundance responses to single and combined environmental stressors revealed several potential molecular mechanisms that could explain a nonadditive increase in heat tolerance of the intertidal copepod <i>Tigriopus californicus</i> when it is simultaneously exposed to high salinity. Protein abundance also follows a generally nonadditive pattern, with only a few exceptions. Furthermore, a number of proteins with putative roles in stress responses exhibit \"emergent\" abundance patterns, in which they only respond to the combined stressors.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"508-524"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a 4-wk high-fat diet on transcriptome and DNA methylation after muscle contractions in rat skeletal muscle.","authors":"Ryo Nehashi, Kentaro Kawata, Yuta Sotani, Tatsuya Kusano, Ryotaro Kano, Reo Takeda, Mizuki Sudo, Yutaka Kano, Daisuke Hoshino","doi":"10.1152/physiolgenomics.00168.2026","DOIUrl":"10.1152/physiolgenomics.00168.2026","url":null,"abstract":"<p><p>Increase in mRNA expression following muscle contraction regulates exercise-induced cellular responses associated with exercise adaptation. However, effects of a high-fat diet (HFD) on muscle contraction-induced alterations in transcription and DNA methylation remain unclear. Therefore, this study aimed to identify the effects of a 4-wk HFD on transcriptomic responses to muscle contractions and to examine the association between these transcriptomic changes and DNA methylation in promoter regions. Rats were fed either an HFD or a normal diet (ND) for 4 wk and underwent electrical stimulation-induced muscle contractions (5 sets × 10 contractions of 3 s at 100 Hz) in the right tibialis anterior (TA) muscle. Both TA muscles were harvested 3 h after muscle contractions for transcriptome and DNA methylation analyses. HFD suppressed the expression of 36 genes, and phosphoprotein was enriched as a Gene Ontology (GO) term. These genes were normally upregulated in response to muscle contractions. Furthermore, myosin heavy chain II, and extracellular matrix were enriched as GO terms for 147 genes that decreased after muscle contractions under HFD conditions, whereas their expression remained unchanged under ND conditions. However, genes whose contraction-induced mRNA expression was altered by HFD were not affected and demonstrated no significant inverse correlation between mRNA expression and DNA methylation levels. Collectively, these results indicate that a 4-wk HFD alters the transcriptomic response of specific GOs associated with muscle contractions, whereas these transcriptomic changes were not accompanied by detectable changes in DNA methylation, at least within the regions captured and analyzed in this study.<b>NEW & NOTEWORTHY</b> This study aimed to identify the effects of a 4-wk HFD on transcriptomic responses to muscle contractions and to examine the association between these transcriptomic changes and DNA methylation in promoter regions. A 4-wk HFD altered the transcriptomic response of specific GOs, including phosphoprotein, MHC II, and extracellular matrix, associated with muscle contractions. However, integrative analysis revealed that these mRNA expression changes were not accompanied by detectable DNA methylation within the regions analyzed in this study.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"493-507"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic basis of pancreatic steatosis: a systematic review of comparison between African and non-African populations.","authors":"Jean Claude Hakizimana, Pelagie Izabayo, M Fatima Leite, Abdullateef Isiaka Alagbonsi","doi":"10.1152/physiolgenomics.00135.2026","DOIUrl":"10.1152/physiolgenomics.00135.2026","url":null,"abstract":"<p><p>This systematic review compared genetic evidence of pancreatic steatosis across African and non-African populations to illuminate ancestry-specific mechanisms and precision-prevention opportunities. Following PRISMA guidelines for reporting, a search was conducted across PubMed, Scopus, Web of Science, and NHGRI-EBI GWAS Catalog for studies spanning 2011 to March 31, 2026. Eligible studies included genome-wide association studies (GWAS), polygenic risk score (PRS), and Mendelian randomization (MR) analyses that reported genetic associations with pancreatic fat phenotypes and had explicit ancestry stratification or comparison. Narrative thematic synthesis was performed due to methodological heterogeneity. Six core genetic studies (<i>n</i> > 120,000 participants) were included. The only multi-ethnic GWAS found a strong protective variant of African ancestry, rs73449607 (near <i>PDX1</i>/<i>PLUTO</i>), which reduced pancreatic fat (β = -0.67, <i>P</i> = 4.50 × 10^-8) and explained 14.3% of the variance in African Americans (vs. 5.3% overall). UK Biobank race-stratified PRS analyses confirmed the lowest pancreatic fat fraction in Black participants, with the strongest HbA1c PRS-fat association in this group (ρ = 0.23, <i>P</i> < 0.0001). European-dominant GWAS highlighted risk loci, including <i>FUT2</i> rs601338 [higher fat and chronic pancreatitis risk, odds ratio (OR) 1.26]. MR studies demonstrated causal links between genetically predicted intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC) (OR 2.46 per SD) but not diabetes. African-ancestry genomes confer substantial protection against pancreatic steatosis, whereas non-African genomes are enriched for risk alleles that amplify the non-alcoholic fatty pancreas disease (NAFPD)-to-PDAC cascade. These ancestry-differentiated mechanisms position NAFPD as a precision medicine target.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"543-551"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiling reveals immunometabolic gene regulation during a 24-h cold exposure survival simulation in humans.","authors":"Jing Zhang, Shawn G Rhind, Michel B DuCharme, Maria Y Shiu, Glen A Selkirk, Michael J Taber, Gregory Walter McGarr, Fabien A Basset, François Haman, Stephen S Cheung","doi":"10.1152/physiolgenomics.00337.2025","DOIUrl":"10.1152/physiolgenomics.00337.2025","url":null,"abstract":"<p><p>Prolonged cold exposure imposes substantial physiological and operational demands; however, the molecular mechanisms supporting human adaptation to sustained cold remain poorly defined. In this first-in-human study, we conducted genome-wide transcriptomic profiling of peripheral blood leukocytes from eight healthy adult males during a 24-h whole body cold survival simulation (7.5°C). Blood samples were collected at four standardized time points to characterize the dynamics of gene expression during continuous cold stress. Despite the clear physiological strain, the global leukocyte transcriptome remained remarkably stable. Differential expression analyses revealed a focused, transient induction of immediate-early genes-including <i>FOS</i>, <i>TAGAP</i>, and <i>TIPARP</i>-primarily associated with standardized exercise bouts performed immediately before and after cold exposure, with expression returning to baseline thereafter. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated activation of immune and stress response signaling pathways (e.g., Toll-like receptor, MAPK, and B-cell receptor signaling) following pre-cold exercise, whereas post-cold sampling was enriched for metabolic pathways, including oxidative phosphorylation and glycolysis/gluconeogenesis, consistent with sustained thermogenic demand and metabolic flexibility. Notably, prolonged cold exposure was not associated with broad inflammatory activation, suggesting that humans maintain transcriptomic homeostasis under sustained cold stress through targeted, energetically efficient immunometabolic regulation. These findings establish peripheral blood as a viable biosampling matrix for monitoring gene-environment interactions during prolonged cold exposure and demonstrate the feasibility of transcriptomic surveillance in extreme environments. Collectively, this study provides foundational systems-level insights into early molecular signatures of human cold resilience and informs the development of blood-based biomarkers, predictive models, and precision countermeasures to support health and performance in Arctic, military, and expeditionary settings.<b>NEW & NOTEWORTHY</b> This first-in-human study provides a systems-level characterization of leukocyte transcriptomic responses to 24-h continuous cold exposure. Despite clear physiological strain, the blood transcriptome remains remarkably stable, with only transient, targeted immunometabolic shifts. These findings reveal energy-efficient molecular homeostasis during sustained cold stress and establish peripheral blood transcriptomics as a viable platform for monitoring human cold adaptation in real-world and operational environments.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"525-542"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel immune-escape signature and classifier for predicting sepsis constructed by integrative bioinformatics.","authors":"Hengling Zhu, Hengbao Zhu, Dongxin Liu, Zaiming Feng, Huihua Li","doi":"10.1152/physiolgenomics.00328.2025","DOIUrl":"10.1152/physiolgenomics.00328.2025","url":null,"abstract":"<p><p>Sepsis is a life-threatening, infection-triggered syndrome of dysregulated inflammation and immune dysfunction. However, the mechanisms underlying immune escape in sepsis remain poorly understood and merit further investigation. Gene expression data for sepsis were obtained from the Gene Expression Omnibus (GEO) database: GSE65682 was used to construct the training cohort, and GSE95233 served as an independent validation cohort. Feature genes were screened by integrating differential expression profiling with Weighted Gene Co-expression Network Analysis (WGCNA). A diagnostic model was developed and validated using receiver operating characteristic (ROC) analysis, a nomogram, and decision curve analysis (DCA). Functional enrichment, immune infiltration, and competing endogenous RNA (ceRNA) network analyses were also performed. Finally, consensus clustering was applied to identify molecular subtypes of sepsis. Three feature genes were identified by differential expression analysis and WGCNA. Area under the curve (AUC)-based screening selected two diagnostic genes (<i>NXT1</i> and <i>UXS1</i>), which demonstrated high diagnostic accuracy (AUC > 0.9). Immune infiltration analysis revealed distinct patterns between the Sepsis and Control groups. Regulatory network analysis identified key miRNAs targeting these two genes and lncRNAs that regulate those miRNAs. Two sepsis subtypes with distinct immune and molecular characteristics were further identified. This study systematically explored the association between immune escape and the pathogenesis of sepsis and, through the integration of multiple bioinformatics approaches, elucidated the immune microenvironmental characteristics and molecular regulatory mechanisms of the disease, providing new insights into understanding its pathophysiology and developing targeted diagnostic and therapeutic strategies.<b>NEW & NOTEWORTHY</b> This study identifies <i>NXT1</i> and <i>UXS1</i> as novel diagnostic biomarkers for sepsis with high predictive accuracy (AUC > 0.9). By integrating differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and immune infiltration, we reveal distinct immune microenvironmental characteristics associated with sepsis pathogenesis. We further define two molecular subtypes of sepsis with heterogeneous immune profiles, providing new insights into immune dysfunction and immune escape in sepsis, which may facilitate the development of targeted diagnostic and therapeutic strategies.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"565-576"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of local CTCF binding impairs renin expression and blood pressure response in Dahl salt-sensitive rats.","authors":"Mark Vanden Avond, Michael N Grzybowski, Terry Kurth, Chun Yang, Jason Klotz, Ana Hantke Guixa, Andrew Greene, Sridhar Rao, Qiongzi Qiu, Pengyuan Liu, Yong Liu, Mingyu Liang, Allen W Cowley, Aron M Geurts","doi":"10.1152/physiolgenomics.00157.2026","DOIUrl":"10.1152/physiolgenomics.00157.2026","url":null,"abstract":"<p><p>Most genetic variants associated with any complex trait are found in non-coding regions. Multiple studies have reported enrichment in single nucleotide polymorphisms (SNPs) found in specific sequences bound by CCCTCF-binding factor (CTCF). CTCF binds DNA to establish boundaries, mediate chromatin interactions and topological domains, and recruit factors to regulate local gene expression. Hypertension is one such disease with enrichment of SNPs in CTCF-binding sites; however, it is not clear whether disruption of CTCF binding to any specific site in the genome could be sufficient to alter blood pressure <i>in vivo</i>. We and others have shown the importance of CTCF-binding and local chromatin interactions governing the renal expression of renin, a critical regulator of systemic blood pressure. Here we developed a model with a mutation to a CTCF-binding motif within first intron of the <i>Ren</i> gene in the Dahl SS rat. CTCF-binding and local chromatin interactions were disrupted, and plasma renin activity (PRA) was impaired when animals were fed a salt-depleted diet in a sex-specific manner, specifically in males. Consistent with the attenuation of PRA, blood pressure was attenuated in male mutant rats during salt depletion. Isolated kidney tissue culture revealed a transcriptional attenuation of <i>Ren</i> expression, suggesting that disruption of CTCF binding within the first intron is critical for initially stabilizing the expression of <i>Ren</i> in response to an inducing stimulus. This is the first demonstration that a mutation to a CTCF-binding site is sufficient to alter a complex physiological trait such as blood pressure regulation, in a sex-specific manner.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cost of Lost Sleep in Menopause: Transcriptional Remodeling of Skeletal Muscle.","authors":"Shadab A Rahman","doi":"10.1152/physiolgenomics.00178.2026","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00178.2026","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Multi-Omics Network by Physical Exercise Across Aging: Molecular Adaptation Beyond Single Signaling Pathways.","authors":"Guilherme da Silva Rodrigues, Ivo Vieira de Sousa Neto, Takuji Kawamura, Ruither de Oliveira Carolino, Ana Paula Pinto, Jessica Denielle Matos Dos Santos, Dennys Esper Cintra, Eduardo Rochete Ropelle, José Rodrigo Pauli, Ellen Cristini de Freitas, Yasuyuki Taki, Zsolt Radak, Adelino Sanchez Ramos da Silva","doi":"10.1152/physiolgenomics.00089.2026","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00089.2026","url":null,"abstract":"<p><p>Aging is characterized by progressive molecular dysregulation across interconnected biological systems, involving alterations in epigenetic regulation, gene expression, protein homeostasis, and metabolic function. Although physical exercise is widely recognized as one of the most effective non-pharmacological interventions to promote healthy aging, the integrative molecular mechanisms underlying its systemic effects remain incompletely understood. This review proposes a multi-omic framework in which exercise acts as a coordinated biological stimulus capable of remodeling age-associated molecular dysfunction across genomic, epigenomic, transcriptomic, proteomic, and metabolomic layers. We discuss evidence showing that exercise modulates DNA methylation patterns associated with inflammation, oxidative stress, and tissue regeneration. Epigenetically, exercise is associated with attenuation of age-associated hypermethylation in promoter regions and modulation of genes involved in oxidative stress defense and tissue regeneration. Transcriptomic studies further show that exercise is associated with more youthful expression patterns while attenuating inflammatory and senescence-related gene programs. Proteomic studies reveal that training is associated with mitochondrial metabolism, extracellular matrix remodeling, and muscle contractile protein abundance, reducing proteostatic dysfunction. Metabolomic analyses demonstrate that exercise improves metabolic flexibility and remodels cellular energy networks. Importantly, the unique contribution of this review lies in synthesizing emerging evidence that these adaptations are highly cell- and tissue-specific, involving immune cells, skeletal muscle satellite cells, endothelial cells, microglia, and intestinal stem cells. Rather than acting through isolated pathways, exercise may induce convergent adaptations across interconnected molecular systems, supporting the concept that healthy aging is dynamically regulated and that age-associated molecular dysfunction retains a degree of biological plasticity.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}