Frontiers in Cell and Developmental Biology最新文献

{"title":"Advances in mechanical force-induced adaptive responses and pathological transition of renal tubular epithelial cells.","authors":"Shilin Li, Yuefeng Cai, Yi Zeng, Zhixia Song, Xisheng Wang","doi":"10.3389/fcell.2026.1981323","DOIUrl":"10.3389/fcell.2026.1981323","url":null,"abstract":"<p><p>Renal tubular epithelial cells (RTECs) reside in a mechanical microenvironment shaped by fluid shear stress, hydrostatic pressure, and cyclic stretch. Under physiological conditions, moderate mechanical stimulation helps maintain normal renal function by regulating cell volume, ion transport, and transcriptional programs. Tubular injury occurs when the intensity or duration of stimulation exceeds physiological tolerance. The balance between protective repair and pathological injury is determined jointly by stimulus intensity, exposure duration, and cellular adaptive capacity. Existing reviews of mechanical stress-induced kidney injury have largely emphasized pathological endpoints. The distinctive contribution of this review is to place the adaptive-to-pathological transition (the threshold at which protective mechanisms fail) and the segmental heterogeneity of tubular mechanoresponses at the center of its framework. We synthesize the molecular mechanisms by which RTECs sense and transduce mechanical signals, with particular emphasis on early adaptive responses including cytoskeletal reorganization, protein quality control, and remodeling of ion homeostasis, and we describe how persistent mechanical stimulation drives the transition from physiological adaptation to pathological injury. We further discuss quantitative and contextual thresholds for this transition, clinically relevant mechanical scenarios beyond classical obstruction, and the phase dependence of mechanosensitive therapeutic targets such as YAP/TAZ. Current research models and technologies are reviewed together with unresolved questions and future directions. By framing mechanically driven kidney disease as a continuum between adaptation and injury, this synthesis provides a theoretical basis for mechanistic studies and for timing-aware, segment-specific clinical translation in mechanical force-related kidney diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1981323"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180484","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":"The m⁶A methyltransferase METTL3 in intervertebral disc degeneration: from molecular mechanisms to therapeutic potential.","authors":"Yi-Chun Zhou, Xiang-Song Xiang, Geng Li, Jian Zhang, Jun Ou","doi":"10.3389/fcell.2026.1949071","DOIUrl":"https://doi.org/10.3389/fcell.2026.1949071","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is the fundamental pathological process underlying low back pain, a major cause leading to disability worldwide. As the most prevalent methylation modification in eukaryotic RNA molecules, N6-methyladenosine (m⁶A) is involved in various diseases and cellular processes by regulating RNA fate. Methyltransferase-like protein 3 (METTL3) is the sole catalytic component of the methyltransferase complex and mediates m⁶A deposition on target RNAs. METTL3 is ubiquitously expressed and modulated by a variety of factors at the transcriptional and post-transcriptional levels. METTL3 expression is significantly increased in degenerative nucleus pulposus tissue and shows a positive correlation with degeneration degree. Importantly, recent studies have demonstrated that METTL3-mediated m⁶A modification is able to promote the progression of IDD through multiple approaches, including extracellular matrix metabolism imbalance, inflammatory response, nucleus pulposus cell senescence and apoptosis, and mitochondrial dysfunction. Thus, METTL3 could represent a promising therapeutic target for IDD. This review systematically summarizes the latest advances regarding the role of METTL3 in IDD and underlying molecular mechanisms, and also highlights its potential translational implications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1949071"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192673","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":"Dynamic three-dimensional chromatin remodeling in lung disease: mechanistic principles, pathogenic regulatory networks, and translational challenges.","authors":"Tiantian Liu, Songshan Jiang, Jing Wang, Jiansheng Li","doi":"10.3389/fcell.2026.1943977","DOIUrl":"https://doi.org/10.3389/fcell.2026.1943977","url":null,"abstract":"<p><p>Three-dimensional (3D) chromatin architecture provides a spatial framework through which genomic sequences, epigenetic states, transcription factors, and distal regulatory elements are integrated to control cell type-specific gene expression. Increasing evidence suggests that disruption of this organization contributes to abnormal transcriptional programs in lung development and disease. In this review, we provide a mechanism-centered synthesis of 3D genome regulation in pulmonary biology, focusing on hierarchical features including A/B compartments, topologically associating domains, chromatin loops, and enhancer-promoter interactions. We discuss how architectural proteins, transcription factors, epigenetic modifications, and regulatory RNAs influence these structures and examine their involvement in chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, and developmental lung abnormalities. Particular emphasis is placed on distinguishing direct evidence of altered chromatin architecture from changes in chromatin accessibility, transcription-factor activity, or epigenetic state that provide regulatory context but do not independently demonstrate 3D genome remodeling. Cross-disease comparison reveals both shared and context-dependent mechanisms, with altered long-range regulatory communication emerging as a recurrent feature while the relevant architectural scale, regulatory factors, cell types, and phenotypic consequences remain disease specific. We further discuss current limitations, including cellular heterogeneity, limited temporal resolution, and the challenge of establishing causality from static interaction maps. Advances in cell type-resolved chromatin conformation profiling, spatial multi-omics, live-cell imaging, and targeted perturbation should enable more precise mechanistic models and clarify whether disease-associated chromatin interactions can ultimately support patient stratification and therapeutic intervention in pulmonary disease.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1943977"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192551","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":"Regulatory mechanisms of programmed cell death in hyperuricaemia and their disease relevance.","authors":"Heng Sai, Haojun Shen, Jing Fu, Wenhui Liu","doi":"10.3389/fcell.2026.1934197","DOIUrl":"https://doi.org/10.3389/fcell.2026.1934197","url":null,"abstract":"<p><p>Hyperuricaemia (HUA) is a metabolic disorder that can not only predispose patients to gout but also be associated with renal, cardiovascular, and metabolic diseases. Recent evidence has designated programmed cell death (PCD) as a central event that drives tissue injury and inflammation in HUA. Raised soluble urate and exposure to monosodium urate (MSU) crystals activate separate but shared stress and injury pathways, including apoptosis, pyroptosis, ferroptosis, and necroptosis in concert with dysregulated autophagy. These processes converge through oxidative stress, mitochondrial dysfunction and signalling along the inflammasome-immune axis to influence disease progression. Among these cell death modalities, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis is a crucial amplifier of urate-induced inflammation and concomitant cellular injury; ferroptosis also contributes to irreversible organ damage along with impaired autophagy. More importantly, extensive crosstalk among these pathways collectively shapes disease trajectory and outcomes. This Review summarises the main regulatory mechanisms that promote PCD during HUA, with a focus on renal injury, cardiovascular damage and metabolic dysregulation. Distinct from pathway-specific summaries, this Review integrates apoptosis, pyroptosis, ferroptosis and necroptosis together with autophagy-related dysfunction into a unified disease-relevance framework linking urate-associated stress, pathway crosstalk and organ-specific injury in HUA. Current limitations and novel therapeutic targets are also discussed to inform basic mechanistic studies together with potential clinical strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1934197"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192587","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":"G3BP1 reduction during cellular senescence promotes SVIL expression and selected senescence-associated phenotypes.","authors":"Hyeong Bin Jeon, Dahyeon Koh, Dohyang Kim, Chaehwan Oh, Yebin Lee, Minjung Lim, Sanghoon Lee, Ji Yun Han, Jae Hong Yoo, Kyung-Seok Han, Myriam Gorospe, Jaewoo Hong, Ji Heon Noh, Kyoung Mi Kim","doi":"10.3389/fcell.2026.1963301","DOIUrl":"10.3389/fcell.2026.1963301","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) can regulate gene expression through multiple post-transcriptional mechanisms, including the control of mRNA stability. In this study, we identified the Ras GTPase-activating protein-binding protein 1 (G3BP1) as a post-transcriptional regulator of <i>supervillin</i> (<i>SVIL</i>) expression. G3BP1 protein levels were consistently reduced across multiple senescence models, whereas <i>SVIL</i> mRNA and SVIL protein levels were increased. RIP analysis showed that <i>SVIL</i> mRNA was associated with G3BP1-containing ribonucleoprotein complexes, and G3BP1 depletion in proliferating cells prolonged the half-life of <i>SVIL</i> mRNA and increased SVIL expression. In particular, SVIL overexpression increased senescence-associated β-galactosidase (SA-β-gal) activity and selectively elevated a subset of senescence-associated secretory phenotype (SASP)-related mRNAs. These findings suggest that reduced G3BP1 expression during senescence contributes to SVIL upregulation through increased <i>SVIL</i> mRNA stability, while elevated SVIL may promote selected senescence-associated phenotypes, including increased expression of SASP-related mRNAs.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1963301"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180464","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":"Expanding the clinical and molecular spectrum of Schaaf-Yang syndrome in China: evidence for a severe phenotypic subgroup associated with <i>MAGEL2</i> c.1996-Region variants.","authors":"Xue-Fei Chen, Shu-Jiong Mao, Sheng Zhong, Shanshan Shen, Xue-Yong Lou, Chao-Chun Zou, Tao Ling","doi":"10.3389/fcell.2026.1932244","DOIUrl":"10.3389/fcell.2026.1932244","url":null,"abstract":"<p><strong>Introduction: </strong>Schaaf-Yang syndrome (SYS) is a rare imprinting-related neurodevelopmental disorder caused by pathogenic variants in the <i>MAGEL2</i> gene. Although the clinical spectrum of SYS has been increasingly recognized, data from Chinese patients remain limited.</p><p><strong>Methods: </strong>We conducted a retrospective questionnaire-based case series to delineate the clinical and molecular characteristics of Chinese individuals with MAGEL2-related disorders among evaluable individuals.</p><p><strong>Results: </strong>We present 28 individuals harboring <i>MAGEL2</i> variants. Developmental delay or intellectual disability was universal. The cohort exhibited the expected multisystem SYS phenotypes, including neonatal hypotonia, feeding difficulties, respiratory involvement, congenital joint contractures, dysmorphic features, endocrine abnormalities, and neurobehavioral manifestations. We identified 23 distinct <i>MAGEL2</i> variants, including 15 novel variants. Fifteen patients carried <i>de novo</i> variants, while 13 had paternally inherited variants, consistent with the imprinting mechanism of SYS. In addition to truncating variants, eight individuals carried missense variants, and their phenotypes appeared to be at the mild end of the SYS spectrum. The <i>MAGEL2</i> c.1996 site was a mutational hotspot, with variants affecting this locus identified in seven patients, including five with the recurrent c.1996dupC variant. Four patients harboring variants at the c.1996 site died of respiratory failure during infancy.</p><p><strong>Discussion: </strong>This study provides the first systematic characterization of Chinese patients with SYS and expands the clinical and molecular spectrum of MAGEL2-related disease. Our findings identify early respiratory dysfunction as a major determinant of disease severity and suggest that truncating variants affecting the <i>MAGEL2</i> c.1996 site might be associated with more severe phenotypes and potentially an increased risk of early mortality. This exploratory observation requires confirmation in larger longitudinal cohorts. Recognition of this genotype-phenotype pattern may help guide early molecular diagnosis, risk assessment, and clinical management in the early life stage of individuals with SYS.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1932244"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180511","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":"Reduced thrombospondin-1 is associated with altered collagen-rich matrix organization in discoid lateral meniscus.","authors":"Shunjie Yang, Chen Hou, Hui Wang, Li Liu, Jian Li, Naihong Yan, Xiaohe Tian, Gang Chen","doi":"10.3389/fcell.2026.1958871","DOIUrl":"https://doi.org/10.3389/fcell.2026.1958871","url":null,"abstract":"<p><p>Discoid lateral meniscus (DLM) is susceptible to tearing and degeneration, but the molecular basis of its altered extracellular matrix (ECM) remains unclear. We integrated histology, electron microscopy, transcriptomics, quantitative proteomics, and donor-derived cell and spheroid models to investigate the association between thrombospondin-1 (THBS1) and matrix organization in symptomatic DLM. Compared with traumatic morphologically normal lateral meniscus (NLM), DLM tissue contained fewer cells per analyzed image (mean difference, -16.10; 95% confidence interval (CI), -23.49 to -8.71; P < 0.0001); lower type-I and II collagen signals; and thinner, less dense, and less organized collagen fibrils. Cross-omics analysis nominated THBS1 and ECM-receptor interaction, and independent assays confirmed a 6.67-fold lower THBS1 protein abundance in DLM (95% CI, 5.04 to 8.27; P < 0.0001). In donor-derived models, THBS1 knockdown in NLM cells reduced area-confluence trajectories, increased migration, and decreased collagen-rich matrix in 4-week spheroids, whereas THBS1 overexpression in DLM cells produced reciprocal changes; aggrecan was not consistently altered. These data associate reduced THBS1 with altered collagen-rich matrix organization and support a functional contribution <i>in vitro</i>. The cross-sectional clinical comparison does not establish chronology, and the spheroid experiments do not demonstrate a fibrillogenesis-specific mechanism.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1958871"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192650","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":"Mechanical regulation of LINC complex function: structural basis, physiological roles, and disease mechanisms in transnuclear mechanotransduction.","authors":"Shuoshuo Shao, Zhu Zhu, Huaiquan Liu","doi":"10.3389/fcell.2026.1946704","DOIUrl":"https://doi.org/10.3389/fcell.2026.1946704","url":null,"abstract":"<p><p>How mechanical stimuli cross the nuclear envelope and are converted into nuclear structural and transcriptional responses is a central question in understanding cellular mechanical adaptation and its failure. The LINC complex is composed of inner nuclear membrane SUN proteins and outer nuclear membrane KASH/Nesprin proteins, and establishes a continuous transnuclear mechanical pathway through its connections with the nuclear lamina and the cytoskeleton. Current evidence indicates that the LINC complex is not a passive molecular bridge. Instead, through SUN-KASH pairing, Nesprin isoforms and perinuclear cytoskeletal linkages, it selects and distributes mechanical inputs from different sources, thereby regulating nuclear positioning, nuclear prestress, nuclear pore transport, chromatin organization and mechanosensitive transcriptional programs. These mechanisms participate in development and in the mechanical adaptation of skeletal and cardiac muscle. When disrupted, they may manifest as global mechanical uncoupling, local stress overload and imbalanced nuclear responses, and are associated with pathological processes including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, neurological disease, premature ageing and tumour invasion. On the basis of this evidence, we propose a continuous framework of \"mechanical input selection, transmembrane force distribution, nuclear response conversion and tissue outcome\" to explain tissue selectivity and phenotypic heterogeneity in LINC-related diseases, and to inform patient variant assessment, disease stratification and precise intervention in aberrant force-transmission pathways.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1946704"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192527","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":"Primordial germ cell-derived macrophages as a platform to study host-pathogen interactions.","authors":"Sudeepta Kumar Panda, Nima Dehdilani, Guillermo Tellez, Ricardo Corona Torres, Lorna Taylor, Charlotte Cody, Samer Halabi, Zhiguang Wu, Rachel Hawken, Mark P Stevens, Mike J McGrew","doi":"10.3389/fcell.2026.1684495","DOIUrl":"https://doi.org/10.3389/fcell.2026.1684495","url":null,"abstract":"<p><strong>Introduction: </strong>Chickens play a crucial role in global food security but are susceptible to a plethora of avian and zoonotic pathogens. Understanding the contribution of pathogen and host factors during infection is important for the design of strategies to control avian diseases, but it is hampered by the lack of reliable and varied avian cell lines for <i>in vitro</i> studies. Macrophages are key components of the innate immune system. They serve as a first line of defense against many infectious agents and help to orchestrate adaptive immune responses. Primary macrophages derived from chickens are limited in number, short-lived in culture, and difficult to genetically manipulate.</p><p><strong>Methods: </strong>Here, we established a protocol where chicken primordial germ cells are differentiated into macrophage-like cells, which provide a continuous <i>in vitro</i> supply of functionally active macrophages.</p><p><strong>Results: </strong>Chicken primordial germ cell-derived macrophages (PGCdMs) had similar molecular, transcriptional, and functional characteristics to chicken bone-marrow-derived macrophages (BMDMs). PGCdMs phagocytosed and killed <i>Salmonella enterica</i> serovar Typhimurium, a zoonotic pathogen commonly transmitted to humans via contaminated poultry products. Moreover, gene-edited PGCdMs were produced by applying CRISPR/Cas9 to the parental PGCs. The knockout of the major signaling molecule MyD88 in PGCdMs revealed that PGCdMs underwent rapid apoptosis after stimulation with lipopolysaccharide.</p><p><strong>Conclusions: </strong>Taken together, chicken PGCdMs will be a valuable cellular resource for studying mechanisms underlying resistance to avian and zoonotic diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1684495"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192675","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":"Quantitative lipidomics reveals Lipid perturbation of plasma apoptotic extracellular vesicles during physiological aging.","authors":"Maojiao Li, Haisen Huang, Qi Tang","doi":"10.3389/fcell.2026.1853081","DOIUrl":"https://doi.org/10.3389/fcell.2026.1853081","url":null,"abstract":"<p><strong>Introduction: </strong>Aging is closely implicated in the pathogenesis of chronic diseases, degenerative conditions, and mortality, making it a core research focus in geroscience. As direct secretory products of apoptotic cells, apoptotic bodies can directly reflect the intensity of apoptotic activity and the degree of systemic and cellular aging. Given their close correlation with senescence progression, apoptotic bodies hold great potential as reliable and sensitive biomarkers for evaluating aging status. However, apoptotic bodies as effective indicators of aging remain to be explored.</p><p><strong>Methods: </strong>We characterized the lipid profile of apoptotic bodies (ApoEVs) and explored the changes in lipid species related to aging. Total lipids, multiple lipid subclasses, and fatty acid saturation within plasma apoptotic bodies were analyzed to identify aging-associated lipid alterations.</p><p><strong>Results and discussion: </strong>A comprehensive reduction in total lipids, multiple lipid subclasses, and fatty acid saturation within plasma apoptotic bodies highlights systemic lipid reprogramming in aging. Decreased total levels of Hex2Cer, LPC, LPE, TG, ChE, SM, and SPH are the features of aging. This study not only deepens the understanding of aging-related lipid dysfunction, but also offers circulating lipid biomarkers for assessing biological aging and age-related pathologies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1853081"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192637","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}