Aging Cell最新文献

{"title":"Podocyte mPGES-2 Determines Renal Aging and Contributes to Senile Osteoporosis","authors":"Dandan Zhong,&nbsp;Chang Hao,&nbsp;Mengyue Li,&nbsp;Jing Liu,&nbsp;Zheng Xu,&nbsp;Jianteng Zhou,&nbsp;Lu Zhao,&nbsp;Siyu Ni,&nbsp;Zhenchao Hu,&nbsp;Yue Sun,&nbsp;Yingying Zou,&nbsp;Dong Sun,&nbsp;Hao Guo,&nbsp;Zhanjun Jia,&nbsp;Dong Guo,&nbsp;Jun-Li Cao,&nbsp;Ying Sun","doi":"10.1111/acel.70609","DOIUrl":"10.1111/acel.70609","url":null,"abstract":"<p>Renal aging shortens healthspan and propagates organ dysfunction beyond the kidney, yet its molecular drivers remain incompletely defined. Here we identify microsomal prostaglandin E synthase-2 (mPGES-2) as a critical regulator of renal aging and its skeletal consequence. Genetic ablation of <i>Ptges2</i> improved health indices in aged mice, prolonged median survival, and markedly alleviated glomerulosclerosis, podocyte injury, and renal senescence. Single-cell transcriptomic analysis, together with podocyte- and tubule-specific knockout models, showed that podocyte mPGES-2, rather than tubular mPGES-2, is the dominant intrarenal driver of aging-related kidney injury. Mechanistically, mPGES-2 promoted podocyte senescence through a PGE₂/EP1 signaling axis. Podocyte-specific <i>Ptges2</i> deletion also mitigated age-related osteoporosis and restored renal calcitriol and α-klotho, supporting a kidney-bone mechanism secondary to impaired renal endocrine function. Consistent with the genetic models, pharmacological inhibition of mPGES-2 with SZ0232 attenuated renal aging and improved bone microarchitecture in aged mice. Both genetic deficiency and pharmacological inhibition of mPGES-2 were well tolerated, with no overt adverse effects on major organs. These findings identify podocyte mPGES-2 as a druggable determinant of renal aging and a potential therapeutic target for aging-associated osteoporosis.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Social Stress Shortens Lifespan in Mice”","authors":"","doi":"10.1111/acel.70604","DOIUrl":"https://doi.org/10.1111/acel.70604","url":null,"abstract":"&lt;p&gt;\u0000 &lt;span&gt;Razzoli, M.&lt;/span&gt;, &lt;span&gt;K. Nyuyki-Dufe&lt;/span&gt;, &lt;span&gt;A. Gurney&lt;/span&gt;, et al. &lt;span&gt;2018&lt;/span&gt;. “ &lt;span&gt;Social Stress Shortens Lifespan in Mice&lt;/span&gt;.” &lt;i&gt;Aging Cell&lt;/i&gt; &lt;span&gt;17&lt;/span&gt;: e12778. https://doi.org/10.1111/acel.12778.\u0000 &lt;/p&gt;&lt;p&gt;The antibody Abcam's ab51243 that is specific for p16-ARC and not for p16&lt;sup&gt;Ink4a&lt;/sup&gt; was erroneously used. This was an unwanted incorrect selection of the antibody since the intent was to measure the p16&lt;sup&gt;Ink4a&lt;/sup&gt; protein.&lt;/p&gt;&lt;p&gt;The results using this antibody did not highlight a significant difference in the liver, and only a non-significant trend for an increase was observed in the spleen of subordinate mice. Therefore, no influential conclusion was drawn based on the use of an inappropriate antibody selection. The conclusion that subordination stress increased markers of cellular senescence was based on a significant change in other markers such as p53 and HMGB1.&lt;/p&gt;&lt;p&gt;Accordingly, the Figure 4 legend, subsection 2.4, the Discussion, and subsection 4.9 should be corrected as follows:&lt;/p&gt;&lt;p&gt;In subsection 2.4, the text “Firstly, we determined the expression of some of the classic cellular markers of senescence including p53, p16&lt;sup&gt;Ink4a&lt;/sup&gt;, HMGB1, and telomere length (Baker et al. 2016; Campisi 2013; Childs et al. 2017) in liver and spleen (organs chosen for showing the highest level of lesions, Figure S2). Subordinate mice showed a significant increase in p53, a tissue-specific significant decrease in HMGB1, and a nearly statistically significant increase in p16&lt;sup&gt;Ink4a&lt;/sup&gt; when compared to dominant mice (Figure 4c,d), while telomere length was similar to the one from dominant subjects (Figure S4).” was incorrect. It should read as follows:&lt;/p&gt;&lt;p&gt;“Firstly, we determined the expression of some of the classic cellular markers of senescence including p53, HMGB1, and telomere length (Baker et al. 2016; Campisi 2013; Childs et al. 2017) in liver and spleen (organs chosen for showing the highest level of lesions, Figure S2). Subordinate mice showed a significant increase in p53, a tissue-specific significant decrease in HMGB1 when compared to dominant mice (Figure 4c,d), while telomere length was similar to the one from dominant subjects (Figure S4).”&lt;/p&gt;&lt;p&gt;In the Discussion, the text “Subordination stress was also associated with the emergence of cellular senescence biomarkers such as increased p53 and decreased HMGB1 (and a nearly statistically significant increase in p16), but not others such as absolute telomere length. […] Nevertheless, the combination of decreased HMGB1 (Davalos et al. 2013) and increased cell cycle inhibitors [p53 and p16&lt;sup&gt;Ink4a&lt;/sup&gt; (Childs et al. 2017)] are in line with the emergence of cellular senescence that can be associated with the development of tissue pathology and earlier mortality in subordinate mice.” was incorrect. It should read as follows:&lt;/p&gt;&lt;p&gt;“Subordination stress was also associated with the emergence of cel","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Primate-Specific lncRNA LINC01021 Contributes to Cellular and Organismal Aging via DAZAP1-Dependent Destabilization of RBMX","authors":"Yan Zhang,&nbsp;Li Hu,&nbsp;Xin Dong,&nbsp;Qinghua Zeng,&nbsp;Meiting Zi,&nbsp;Ayesha Nisar,&nbsp;Sawar Khan,&nbsp;Raoxian Bai,&nbsp;Chonghui Liu,&nbsp;Mingxia Ge,&nbsp;Shaoyan Pu,&nbsp;Gonghua Li,&nbsp;Yonghan He","doi":"10.1111/acel.70603","DOIUrl":"10.1111/acel.70603","url":null,"abstract":"<p>Aging is characterized by progressive physiological decline and age-related pathologies, yet the molecular determinants underlying lineage- and species-specific aging traits remain poorly understood. Although protein-coding regulators have dominated aging research, the contribution of long non-coding RNAs (lncRNAs), particularly primate-specific lncRNAs, has not been systematically explored. Here, through evolutionary screening and cross-species aging-associated analyses, we identified a set of primate-specific lncRNAs (including <i>LINC01021</i>, <i>CTC-575 l10.1</i>, <i>CTA-150C2.13</i>, and <i>RP11-305F18.1</i>, etc.) associated with human aging, and we functionally characterized <i>LINC01021</i> as a representative candidate to assess their causal involvement. In human cells, <i>LINC01021</i> promotes cellular senescence, whereas its silencing attenuates senescence-associated phenotypes. Mechanistically, <i>LINC01021</i> is predominantly located in the nucleus, where it facilitates DAZAP1-dependent destabilization of RBMX mRNA, leading to activation of the P53 pathway and induction of canonical senescence features. At the organismal level, ectopic expression of human <i>LINC01021</i> in mice contributes to aging-like phenotypes, including increased frailty and impaired motor coordination. Together, these findings implicate primate-specific lncRNAs in lineage-restricted aging and highlight an evolutionarily recent regulatory layer that may modulate aging trajectories.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Environmental Enrofloxacin Exposure as a Modifiable Driver of Mitochondria-Mediated Intestinal Aging and Barrier Dysfunction”","authors":"","doi":"10.1111/acel.70598","DOIUrl":"https://doi.org/10.1111/acel.70598","url":null,"abstract":"<p>\u0000 <span>Yu, K.</span>, <span>N. Wang</span>, <span>X. Huang</span>, et al. (<span>2026</span>). <span>Environmental Enrofloxacin Exposure as a Modifiable Driver of Mitochondria-Mediated Intestinal Aging and Barrier Dysfunction</span>. <i>Aging Cell</i> <span>25</span>, no. <span>5</span>: e70526. https://doi.org/10.1111/acel.70526.\u0000 </p><p>In the legend of Figure 6, the first sentence, “Impact of ENR exposure on zebrafish intestinal epithelial cells,” was incorrect. This should have read: “Impact of ENR exposure on rat intestinal epithelial cells.” The correct figure is as follows:</p><p>In Figure 9J, the merged images for the Ctrl and ENR groups in the Merge column were inadvertently placed in the wrong order during figure preparation. The correct figure is as follows:</p><p>These errors were introduced during the figure assembly process and do not affect the corresponding single-channel images, the ENR+PQQ group, the quantitative analysis shown in Figure 9K, or the conclusions of the article.</p><p>We apologize for these errors.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The LAV-BPIFB4-Platelet-CD47 Axis: A Novel Mechanism Associated With Immune Resilience in Longevity","authors":"Elena Ciaglia,&nbsp;Roberta Maria Esposito,&nbsp;Valentina Lopardo,&nbsp;Francesco Montella,&nbsp;Cristina Basile,&nbsp;Roberta Longo,&nbsp;Anna Maciag,&nbsp;Giuseppe Rescigno,&nbsp;Antonio Damato,&nbsp;Francesco Del Plato,&nbsp;Alfonso Finizio,&nbsp;Carmine Vecchione,&nbsp;Albino Carrizzo,&nbsp;Annibale Alessandro Puca","doi":"10.1111/acel.70602","DOIUrl":"10.1111/acel.70602","url":null,"abstract":"<p>Long-living individuals (LLIs) possess remarkable genetic resilience, characterized by protective variants that confer immune robustness and resistance to age-related diseases. The longevity-associated variant of BPIFB4 (LAV-BPIFB4), enriched in centenarians, demonstrated pleiotropic benefits including reduced inflammation, cardiovascular protection, and immune system rejuvenation. However, the molecular mechanisms underlying these protective effects remain incompletely understood. Here, we revealed that LAV-BPIFB4 fundamentally reshaped the immune features of platelets to establish enhanced immunomodulatory capacity through CD47 upregulation. Of note, centenarians displayed an elevated percentage of circulating CD47⁺ reticulated platelets (RPs), a condition mimicked by LAV-BPIFB4 carriers which exhibited significantly elevated CD47 levels both on RPs and mature platelets' surface. In agreement with an early acquirement of CD47 overexpression, MEG-01 megakaryoblastic cells overexpressing LAV-BPIFB4 produced CD47-high platelet-sized particles. Functionally, platelets from LAV carriers suppressed monocyte activation and inflammatory cytokine production through CD47-dependent mechanisms, selectively reducing p38 MAPK activation while leaving NF-κB signaling largely unaffected in response to LPS. rhLAV-BPIFB4 administration in vivo increased CD47 on murine platelets and reduced, ex vivo, LPS-induced monocyte activation, validating cross-species therapeutic potential. Critically, rhLAV-BPIFB4 protein phenocopies genetic effects, rapidly increasing CD47 expression on wild-type platelets through cytoskeleton-dependent trafficking mechanisms and conferring enhanced anti-inflammatory capacity. This might represent a translatable strategy to replicate some of the biological features associated with a longevity-associated variant beyond genetic carriers. Our findings establish the platelet-CD47-monocyte axis as a pivotal pathway for healthy aging and reveal recombinant LAV-BPIFB4 as a promising therapeutic approach for managing inflammaging and cardiovascular disease by harnessing the immune-tuning capacity characteristic of exceptional longevity.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice”","authors":"","doi":"10.1111/acel.70611","DOIUrl":"10.1111/acel.70611","url":null,"abstract":"<p>\u0000 <span>Cong, P.</span>, <span>X. Huang</span>, <span>Q. Zhang</span>, et al. <span>2025</span>. “ <span>DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice</span>.” <i>Aging Cell</i> <span>24</span>: e14458. https://doi.org/10.1111/acel.14458.\u0000 </p><p>In Figure 3I, the <i>x</i>-axis group labels were missing below the rightmost fEPSP amplitude quantification bar graph, and the EGFP and shDnmt3a groups in this bar graph were mistakenly labeled with incorrect colors during figure assembly. The corrected image is provided here. This correction does not affect the underlying data, statistical analysis, interpretation of the results, or conclusions of the study.</p><p>We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Non-Channel Function of CFTR: Attenuating Mitochondrial Oxidative Stress and Cardiomyocyte Senescence via Stabilization by USP45","authors":"Chun Chen,&nbsp;Longtan Jiang,&nbsp;Yuewen Qiu,&nbsp;Chong Liu,&nbsp;Xiao Long,&nbsp;Pengcui Wu,&nbsp;Liang Li,&nbsp;Haixia Xu,&nbsp;Ping Deng,&nbsp;Li Yang,&nbsp;Qiao Jin","doi":"10.1111/acel.70610","DOIUrl":"https://doi.org/10.1111/acel.70610","url":null,"abstract":"<p>Cardiomyocyte senescence drives cardiovascular disease, underscoring the need to define its molecular mechanisms. The role of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in this process remains unclear, particularly regarding its expression and function. Atrial tissues were collected from patients with sinus rhythm or atrial fibrillation (AF) of varying durations. CFTR was downregulated in AF patients and negatively correlated with p16, p21, and p53. Myocardial aging models were established using D-galactose (D-gal) in both mice and neonatal mouse cardiomyocytes (CMs). In both animal and cellular models, D-gal increased SA-β-gal positivity and senescence markers while decreasing CFTR. Overexpressing CFTR reduced D-gal-induced elevations in p16, p21, p53, and malondialdehyde (MDA), and restored superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities. Mechanistically, CFTR alleviates mitochondrial oxidative stress damage by enhancing plasma membrane Ca²⁺ ATPase (PMCA) activity to reduce cytoplasmic Ca²⁺ levels. Furthermore, we identified USP45 as a direct binding partner of CFTR, which deubiquitinates CFTR by specifically targeting K48-linked chains and the K688 residue. CFTR knockdown exacerbated D-gal-induced senescence and mitochondrial oxidative stress, which was rescued by USP45 overexpression. In conclusion, this study reveals a novel mechanism in which USP45-mediated deubiquitination of CFTR mitigates cardiomyocyte senescence and mitochondrial oxidative stress, offering a targeted intervention against age-related cardiovascular diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Hypoxia-Inducible Factor 1-Alpha Accumulation Disrupts the Articular Niche to Promote Osteoarthritis Pathogenesis","authors":"Weiyuan Gong,&nbsp;Chu Tao,&nbsp;Xingyun Wang,&nbsp;Rongdong Liao,&nbsp;Jianglong Li,&nbsp;Xiongtian Guo,&nbsp;Minghao Qu,&nbsp;Jianmei Huang,&nbsp;Mingjue Chen,&nbsp;Fuxin Wei,&nbsp;Peng Wang,&nbsp;Lijun Lin,&nbsp;Di Chen,&nbsp;Qing Yao,&nbsp;Chunyi Wen,&nbsp;Guozhi Xiao","doi":"10.1111/acel.70606","DOIUrl":"10.1111/acel.70606","url":null,"abstract":"<p>The precise role of hypoxia-inducible factor-1α (HIF-1α) in osteoarthritis (OA) pathogenesis remains controversial, often debated between a protective compensatory factor and a disease mediator. Here, we demonstrate that sustained, uncoupled HIF-1α accumulation functions as a potent, compartment-specific pathogenic driver of joint destruction. Using genetically engineered mouse models, we reveal that chondrocyte-specific HIF-1α overexpression (<i>Acan</i>^{<i>CreERT2</i>}; <i>Hif1αdPA</i>^<i>fl/fl</i>) triggers spontaneous OA and exacerbates destabilization of the medial meniscus (DMM)-induced post-traumatic joint degeneration. Mechanistically, continuous HIF-1α activation drives pathological angiogenesis that physically dismantles the avascular, hypoxic cartilage niche, forcing a profound metabolic dysregulation that culminates in catastrophic matrix degradation. Conversely, sustained HIF-1α activation within the synovial and superficial cartilage compartments (<i>Prg4- GFPCreERT2</i>; <i>Hif1αdPA</i>^<i>fl/fl</i>) drives a slowly progressive, late-onset spontaneous OA through chronic inflammatory accumulation that actively suppresses Col2a1 expression. Furthermore, this robust inflammatory priming establishes a highly vulnerable microenvironment, whereby DMM surgery significantly accelerates the progression of trauma-induced joint collapse. Finally, transient whole-joint HIF-1α induction via an intra-articular injection of lipid nanoparticles (LNP-mRNA) closely recapitulates these detrimental effects. Collectively, our study reconciles existing controversies by establishing sustained HIF-1α accumulation as a spatiotemporally dynamic, broad disease amplifier across the articular ecosystem, highlighting its targeted inhibition as a promising therapeutic strategy for OA.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Heterogeneity During Arterial Aging","authors":"He Xu,&nbsp;Paul-Lennard Mendez,&nbsp;Dimitri Kasakovski,&nbsp;Judith Sluimer","doi":"10.1111/acel.70597","DOIUrl":"https://doi.org/10.1111/acel.70597","url":null,"abstract":"<p>Arterial aging is a major risk factor for cardiovascular disease and is associated with progressive changes in vascular structure and function, including arterial stiffening, reduced elasticity, extracellular matrix remodeling, chronic low-grade inflammation, and accumulation of senescence-associated cell states. Recent advances in single-cell RNA sequencing (scRNA-seq) have provided new opportunities to resolve the cellular heterogeneity underlying these age-related alterations in the arterial wall. In this review, we summarize current single-cell studies of arterial aging by focusing first on key phenotypic programs, including cellular senescence, extracellular matrix remodeling, inflammaging, and altered intercellular communication, and then discuss how these programs are reflected in endothelial cells, smooth muscle cells, fibroblasts, and immune cells. Across studies, aging is recurrently associated with endothelial dysfunction, smooth muscle cell phenotypic modulation, fibroblast-related matrix remodeling, and immune activation, although the degree of conservation varies depending on species, vascular bed, sex, and disease context. We further discuss emerging evidence that vascular aging involves not only cell-intrinsic transcriptional changes but also alterations in communication networks across the arterial wall. Although current single-cell studies have substantially improved our understanding of arterial aging, important limitations remain, including inconsistent cell-state annotation across studies, incomplete functional validation, and limited spatial and epigenetic resolution. Future integration of cross-species analyses with spatial transcriptomics, single-cell epigenomic approaches, and functional studies will help refine the cellular framework of arterial aging and improve its translational relevance.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Induced Senescent Macrophage-Driven Squamous Cell Carcinoma Invasion via Glutamine Metabolic Reprogramming","authors":"Shimeng Wang,&nbsp;Jingtian Mu,&nbsp;Wei Zhao,&nbsp;Can Hu,&nbsp;Xueke Shi,&nbsp;Hongmei Zhou,&nbsp;Junjiang Liu,&nbsp;Fanglong Wu","doi":"10.1111/acel.70592","DOIUrl":"https://doi.org/10.1111/acel.70592","url":null,"abstract":"<p>Oxidative stress drives tumor microenvironment (TME) remodeling by inducing metabolic reprogramming and cellular senescence. Glutamine, a key substrate supporting oxidative stress defense, has been implicated in TME remodeling and metastasis, yet its specific role in initiating tumor invasion remains unclear. Here, oxidative stress induced the generation of senescent macrophages in the TME, and clinical samples showed that their accumulation positively correlates with malignancy. We established cisplatin- and radiation-induced senescent macrophage models that exhibited distinct senescence-associated secretory phenotypes (SASP) and enhanced squamous cell carcinoma (SCC) migration and invasion. Integrated metabolomic and transcriptomic analyses revealed the glutamine–glutamate pathway as a central metabolic hub, with glutaminase 2 upregulated to drive glutaminolysis and strongly associated with IL-1β expression. Mechanistically, IL-1β secreted by senescent macrophages promoted tumor invasion by downregulating IL-1R2 and activating NF-κB signaling in SCC cells. Targeting the glutamine metabolism–regulated IL-1β/IL-1R2 axis effectively suppressed SCC invasion. These findings uncover a novel metabolic mechanism linking glutamine metabolism to SASP regulation and suggest a therapeutic strategy to limit SCC invasion.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 7","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}