Aging Cell最新文献

{"title":"Correction to “Age-Related Alterations in Hippocampal Microstructure Quantified Using High-Gradient Diffusion MRI (dMRI) in an Unfolded Hippocampal Space”","authors":"","doi":"10.1111/acel.70654","DOIUrl":"10.1111/acel.70654","url":null,"abstract":"<p>\u0000 <span>Ma, Y.</span>, <span>H. Lee</span>, <span>K.-S. Chan</span>, et al. <span>2026</span>. “ <span>Age-Related Alterations in Hippocampal Microstructure Quantified Using High-Gradient Diffusion MRI (dMRI) in an Unfolded Hippocampal Space</span>.” <i>Aging Cell</i> <span>25</span>, no. <span>1</span>: e70274. https://doi.org/10.1111/acel.70274.\u0000 </p><p>The Conflicts of Interest section should be updated as follows:</p><p>Dr. Salat has a financial interest in Niji Corp.</p><p>We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662930","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":"Diosgenin Alleviates Age-Related Sarcopenia by Promoting Satellite Cell Proliferation and Myogenic Differentiation via Activation of the SIRT1/PGC-1α Signaling Pathway","authors":"Xin Zeng,&nbsp;Han Ding,&nbsp;Ziye Li,&nbsp;Qian Wang,&nbsp;Peiyao Guan,&nbsp;Tingting Wang,&nbsp;Jiayun Wang,&nbsp;Yansong Fu,&nbsp;Lizhang Chen,&nbsp;Hong Qin","doi":"10.1111/acel.70651","DOIUrl":"https://doi.org/10.1111/acel.70651","url":null,"abstract":"<p>Age-related sarcopenia is characterized by a progressive decline in skeletal muscle mass and function, with satellite cell dysfunction representing a central pathogenic mechanism. Diosgenin, a steroidal saponin derived from plants of the <i>Dioscorea</i> genus, has demonstrated potential anti-aging properties; however, its role in sarcopenia remains unclear. In this study, naturally aged C57BL/6J mice and a D-galactose (D-gal)–induced senescent C2C12 cell model were employed to systematically investigate the effects of diosgenin on muscle function, satellite cell dynamics, and the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway. Diosgenin treatment significantly improved forelimb grip strength and exercise endurance, increased the gastrocnemius muscle index, and enlarged muscle fiber cross-sectional area in aged mice. Mechanistically, diosgenin upregulated the expression of myokines meteorin-like protein (METRNL) and insulin-like growth factor 1 (IGF-1) at both mRNA and protein levels, increased the number of proliferative satellite cells positive for paired box 7 (Pax7) and Ki67, and enhanced the expression of myogenic markers, including myogenic factor 5 (Myf5), Pax7, and myosin heavy chain II (MyHC II). These effects were mediated by direct activation of SIRT1, leading to deacetylation of PGC-1α. Notably, pharmacological inhibition of SIRT1 with EX527 markedly abrogated the diosgenin-induced effects. Molecular docking and cellular thermal shift assays further confirmed the direct interaction between diosgenin and SIRT1. Collectively, these findings demonstrate that diosgenin alleviates age-related sarcopenia by activating the SIRT1/PGC-1α signaling pathway to promote satellite cell proliferation and myogenic differentiation, highlighting its potential as a promising therapeutic candidate for sarcopenia.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617209","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":"Progerin Hinders Autophagy Flux at Its Final Stages in Hutchinson-Gilford Progeria Syndrome Cells, Preventing Its Own Autophagic Degradation","authors":"Ian García-Aguirre,&nbsp;Jesús Alejandro Reyes-Martínez,&nbsp;Juan Unzueta,&nbsp;Francisco Guevara-Namorado,&nbsp;Solangy Lizcano-Meneses,&nbsp;Susana Gonzalo,&nbsp;Angel Baldan,&nbsp;Claudia Rangel,&nbsp;Gerardo J. Alanis-Funes,&nbsp;Francisco Garcia-Sierra,&nbsp;Kevin Ruiz-Fajardo,&nbsp;Simon Gormes-Pinchanski,&nbsp;Susana Castro-Obregón,&nbsp;Aranza Meza-Dorantes,&nbsp;Rocio Alejandra Chavez-Santoscoy,&nbsp;Isabel Arrieta-Cruz,&nbsp;Paola Tristán-Aburto,&nbsp;Jonathan J. Magaña,&nbsp;Bulmaro Cisneros","doi":"10.1111/acel.70649","DOIUrl":"https://doi.org/10.1111/acel.70649","url":null,"abstract":"<p>In Hutchinson-Gilford progeria syndrome (HGPS), dysfunctional autophagy results in the accumulation of progerin, a lamin A mutant variant that alters a plethora of processes, inducing senescence and driving premature aging. Therefore, the elimination of progerin through autophagy restoration emerges as a therapeutic intervention against HGPS. However, a comprehensive study of autophagy flux in HGPS remains to be addressed. In this study, the dynamics of autophagy in HGPS fibroblasts were analyzed utilizing different HGPS cell models and experimental approaches. The autophagy-associated transcriptomic profile was determined, and the autophagy-lysosome axis was comprehensively analyzed. We demonstrated that progerin induces the formation of autophagosomes but impairs their maturation and subsequent fusion with lysosomes. This alteration is attributed in part to the progerin-mediated decreased expression of STX17, a marker of mature autophagosomes, and LAMP1, a membrane lysosomal protein, as well as the presence of defective lysosomes. In line with this, the rescue of STX17 and LAMP1 expression improved autophagy flux. Interestingly, treatment of HGPS fibroblasts with Selinexor, an autophagy activator, elicited nuclear accumulation of TFEB and enhanced lysosomal biogenesis and function, thereby activating autophagy. Selinexor treatment improved both autophagosome maturation and autophagosome-lysosome fusion, which ultimately led to effective autophagic degradation of progerin. In summary, progerin impedes proper autophagy flux, thus preventing its own autophagic degradation, which underscores the relevance of targeting the autophagy-lysosome pathway to counteract the toxic accumulation of progerin.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616512","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":"Biological Versus Technical Reliability of Epigenetic Clocks and Implications for Disease Prognosis and Intervention Response","authors":"Raghav Sehgal,&nbsp;Daniel S. Borrus,&nbsp;John Gonzalez,&nbsp;Yaroslav Markov,&nbsp;Albert Higgins-Chen,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1111/acel.70635","DOIUrl":"https://doi.org/10.1111/acel.70635","url":null,"abstract":"<p>Epigenetic clocks are widely used to estimate biological age and predict health outcomes, but their translational value depends not only on accuracy but also on reliability. Using the TranslAGE platform, we evaluated both technical and biological reliability across 18 DNA methylation–based aging biomarkers, including chronological, mortality, and pace-of-aging clocks. Most clocks demonstrated excellent technical reproducibility across replicate assays on EPIC and 450 K arrays. However, several showed sensitivity to experimental factors such as slide position and DNA extraction protocols. In contrast, PC-based clocks, particularly PCGrimAge and SystemsAge, remained robust across conditions. Biological reliability, assessed across repeated measures collected within short intervals under varying conditions such as meals, stress, and environmental exposures, was substantially lower. Most clocks showed only low to moderate stability which further decreased when adjusting for immune composition. Notably, technical reproducibility did not predict biological reliability. We further show that reliability directly impacts downstream applications. Clocks with higher reliability produced more stable associations with cognitive outcomes and more consistent responses to interventions, while less reliable clocks yielded variable or misleading results. These findings highlight a critical limitation in current epigenetic clocks. Improving biological reliability will be essential for advancing their use in clinical and interventional settings.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616513","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":"Metabolic Signatures of Aging and Gametogenesis in Hydra oligactis","authors":"Nicki Marami-Zonouz,&nbsp;Erwann Arc,&nbsp;Thomas Roach,&nbsp;Pidder Jansen-Dürr,&nbsp;Werner Bader,&nbsp;Bert Hobmayer,&nbsp;Ilse Kranner","doi":"10.1111/acel.70643","DOIUrl":"10.1111/acel.70643","url":null,"abstract":"<p>Aging can be experimentally induced in <i>Hydra oligactis</i>, making it an exception among the “immortal” cnidarian genus <i>Hydra</i>. In response to cold temperatures, <i>H. oligactis</i> polyps switch from asexual to “emergency” sexual reproduction and eventually age and die. We used GC–MS-based metabolite profiling to characterize cold-induced (CI) metabolic reprogramming during concurrent sexual differentiation and aging in <i>H. oligactis</i>. Metabolites in four clusters either decreased or increased progressively until week 8, when animals were severely aged, whereas others peaked at sexual maturity after 4–6 weeks. At week 4, signatures of failing cytoprotection and neurotransmitter function appeared in both sexes, including a drastic reduction of taurine, whose deficiency is a known driver of aging in other organisms. Taurine supplementation partly reversed interstitial stem cell loss during the first 2 weeks of cold induction and subsequent sexual differentiation. Metabolites in the NAD⁺ synthesis and salvage pathways, such as picolinate and niacin, also declined. Changes in pyruvate and TCA cycle intermediates indicated increased energy demands associated with both gametogenesis and aging. Urate, the final oxidation product of purine metabolism, showed the highest fold-change, peaking at sexual maturity in both sexes and remaining elevated. The abundance of most purine and pyrimidine bases also increased, in line with nucleotide cleavage by apoptosis, as part of gametogenesis and aging. Sexual maturity was clearly reflected by high levels of polyamines, such as putrescine, cadaverine, and 3-hydroxybutyrate, required for spermatogenesis. Our study reveals metabolic processes related to gametogenesis and aging and highlights differences between female and male metabolism.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589794","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":"Unveiling the AcSirt2-FOXO-Mitophagy Axis: Insights Into Mitochondrial Quality Control and Delayed Aging in Apis cerana","authors":"Qiang Ma,&nbsp;Zhengang Ma,&nbsp;Tingyue Huang,&nbsp;Qianmin Hai,&nbsp;Xiaoqun Dang,&nbsp;Jinshan Xu,&nbsp;Jialing Bao,&nbsp;Zachary Y. Huang,&nbsp;Zeyang Zhou","doi":"10.1111/acel.70645","DOIUrl":"10.1111/acel.70645","url":null,"abstract":"<p>Cellular senescence is closely associated with mitochondrial dysfunction. Sirtuin 2 (Sirt2), a member of the Sirtuin deacetylases family, plays a pivotal role in regulating energy metabolism and aging in mammals. However, its function in social insect aging remains unclear. Here, using the Eastern honey bee (<i>Apis cerana</i>) as a model, we demonstrate that the age-related downregulation of <i>A. cerana</i> Sirt2 (<i>AcSirt2</i>) in brain tissue is coupled with progressive mitochondrial damage, reactive oxygen species (ROS) accumulation, and a biphasic change in autophagy activity. Conversely, overexpression of AcSirt2 alleviates cellular senescence by promoting mitochondrial fusion/fission balance (via Mfn1, Mfn2, and Drp1), activating the PINK1/Parkin-mediated mitophagy pathway, improving mitochondrial integrity, reducing oxidative stress, and enhancing ATP production. In vivo, AcSirt2 knockdown shortens honey bee lifespan and impairs locomotor ability, whereas its activation reverses these aging phenotypes. Furthermore, we show that AcSirt2 interacts with the transcription factor FOXO and mediates its deacetylation. This study reveals for the first time that the AcSirt2-FOXO-mitophagy axis delays aging by maintaining mitochondrial homeostasis in a social insect, providing novel insights into the development of anti-aging strategies and the promotion of healthy beekeeping.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589749","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":"Construction and Validation of Plasma Protein-Based Musculoskeletal Biological Age and Genetic and Environmental Risk Profiles","authors":"Yangdan Zhong,&nbsp;Maoyao Xia,&nbsp;Xunying Zhao,&nbsp;Yang Qu,&nbsp;Bowen Lei,&nbsp;Sirui Zhen,&nbsp;Tao Han,&nbsp;Rong Xiang,&nbsp;Jinyu Xiao,&nbsp;Xin Song,&nbsp;Xiaofeng Ma,&nbsp;Bin Yang,&nbsp;Di Zhang,&nbsp;Jinyu Zhou,&nbsp;Zilan Chen,&nbsp;Yuqi Pang,&nbsp;Ye Ju,&nbsp;Ting Liu,&nbsp;Zihao Li,&nbsp;Lu Long,&nbsp;Tao Zhang,&nbsp;Jiayuan Li,&nbsp;Mengyu Fan,&nbsp;Zuyun Liu,&nbsp;Xia Jiang","doi":"10.1111/acel.70636","DOIUrl":"https://doi.org/10.1111/acel.70636","url":null,"abstract":"<p>The musculoskeletal system is key to aging. Nonetheless, existing protein-based musculoskeletal aging clocks have limited predictive performance and fail to characterize genetic or environmental determinants. We first constructed a musculoskeletal protein pool by integrating transcriptomic enrichment, protein functional annotation, and literature expertise. Two musculoskeletal aging clocks—MSKAge and MSKAgeMort—were then developed using proteomic data of 21,070 UK Biobank participants. Acceleration metric (MSKAgeAccel/MSKAgeMortAccel) quantified deviations of biological age from chronological age, with positive values indicating accelerated musculoskeletal aging. Associations of MSKAgeAccel/MSKAgeMortAccel with mortality, musculoskeletal disorders, and age-related diseases were assessed using Cox proportional hazards models. Environmental and genetic determinants were evaluated by linear regression and genome-wide association analyses, respectively. Drug repurposing was used to identify potential targets of musculoskeletal diseases. A total of 39 musculoskeletal-related proteins constituted the pool. Leveraging these proteins, MSKAge (<i>r</i>_female = 0.62; <i>r</i>_male = 0.56) and MSKAgeMort (<i>r</i>_female = 0.93; <i>r</i>_male = 0.88) were constructed. Both MSKAgeAccel and (in particular) MSKAgeMortAccel predicted mortality, musculoskeletal diseases, and age-related diseases effectively. MSKAgeMortAccel showed significant associations with musculoskeletal disorders, including osteoarthritis, rheumatoid arthritis, gout, and low back pain. MSKAgeMortAccel was influenced by environmental pollutants, psychological factors, and unhealthy lifestyles. Genetic analyses revealed 13 variants and 71 genes enriched in epigenetic regulation and extracellular environment-receptor interaction. Zinc was identified as a candidate musculoskeletal drug. We established a reliable musculoskeletal aging clock and elucidated genetic and environmental determinants. This framework enables stratification of individuals at risk of accelerated musculoskeletal aging, paving the way for anti-aging interventions.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615864","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":"Single Cell and Spatially Resolved Transcriptome and Immune Repertoire of Mouse Thymus During Aging Reveal Immunological Heterogeneity and Direction of Thymic Selection Pressure","authors":"Jialing Fang,&nbsp;Jun Lei,&nbsp;Peng Chen,&nbsp;Zaiqiao Sun,&nbsp;Boxiao He,&nbsp;Yankang Wu,&nbsp;Chonil Paek,&nbsp;Ning Wu,&nbsp;Yafei Huang,&nbsp;ZhaoKui Dan,&nbsp;Hui Zhang,&nbsp;Zijing Xu,&nbsp;Pengcheng Wei,&nbsp;Yongshun Chen,&nbsp;Lei Yin","doi":"10.1111/acel.70631","DOIUrl":"10.1111/acel.70631","url":null,"abstract":"<p>The thymus is the central organ where T cells differentiate and proliferate. T cells experience the TCR recombination to generate diversity, self-antigen tolerance, and immune response. However, the spatial heterogeneity of transcriptomics and immune repertoire of the thymus during aging haven't been studied. We constructed the thymus's spatial transcriptomics and spatial immune repertoire atlas by TCR-specific amplification. The integrated multi-omics analysis of the scRNA-seq, ST-seq, spatial-TCR-seq, scTCR-seq, and TCR-seq was developed to investigate the thymus during aging. ST-seq demonstrated that the heterogeneity of the cortex and a novel cortex subset associated with progenitor cell differentiation was identified. Proliferating CD69negDN T cells decreased and regulatory CD4SP T cells increased during aging. Using deconvolution analyses, the spatial distribution of T cell subsets was revealed. The spatial distribution of TCR recombination and distinct thymic selection processes were illustrated. Pseudo-time analyses demonstrated differentiation order and spatial migration route of T cells. The novel spatial-TCR-seq demonstrated the overall spatial distribution of TCR, the TCR pairing process, and their dynamic features under thymic selection pressure which revealed that TRB clonotypes with hydrophilic and low-pI CDR3s tended to pass the negative selection opposite to the positive selection. The positive selection pressure of the thymus diminishes during the aging process. A TCR maturation scoring system using TCR-seq was developed to identify TCR clonotypes that tended to mature. All boost the thymus study into the era of spatial immune repertoire and transcriptome and widen our knowledge about T cell development.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589804","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":"Apiotrichum-Centered Fungal Interaction Network Disturbance Correlates With Increased Arterial Stiffness","authors":"Jiarui Chen,&nbsp;Jialin He,&nbsp;Bingqi Ye,&nbsp;Jialu Yang,&nbsp;Ludi Liu,&nbsp;Jingmeng Ju,&nbsp;Sinan Li,&nbsp;Benjie Li,&nbsp;Min Xia,&nbsp;Yan Liu","doi":"10.1111/acel.70650","DOIUrl":"10.1111/acel.70650","url":null,"abstract":"<p>The gut mycobiome plays an essential role in human health, yet its influence on the progression of arterial stiffness, a key feature of vascular aging, remains obscure. In this study, we aimed to investigate the involvement of intestinal fungi in the exacerbation of arterial stiffness. In total, 763 participants were invited for the brachial-ankle pulse wave velocity test to determine their status of arterial stiffness. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping arrays, and plasma metabolites were quantified using untargeted liquid chromatography-mass spectrometry. A less clustered but more communicative fungal community was found in individuals with elevated stiffness. Five driving fungal genera contributing to the shift of fungal interaction networks from normal to elevated stiffness, including <i>Apiotrichum</i>, <i>Mycothermus</i>, <i>Flavocillium</i>, <i>Hyaloscypha</i>, and <i>Microscypha</i>, were associated with arterial stiffness. Integrative analysis with metabolomics further demonstrated that organic acids, fatty acyls, and alkaloids mediated the effect of <i>Apiotrichum</i>, <i>Mycothermus</i>, and <i>Microscypha</i> on arterial stiffness. Moreover, alpha-1A adrenergic receptor, alpha-2B adrenergic receptor, cytochrome P450 Family 11 subfamily B member 2, angiotensin I converting enzyme, angiotensin II receptor type 1, matrix metallopeptidase 2, tumor necrosis factor, and rho-associated coiled-coil containing protein kinase 2 were identified as the key molecular transducers associated with increased <i>Apiotrichum</i> in arterial stiffness. Our study uncovers a strong association between disruption in gut fungi and the progression of elevated arterial stiffness, and highlights the potential of targeting the gut mycobiome for improving vascular health.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589822","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":"Neutrophil Extracellular Traps Exacerbate UVB-Induced Photodamage in HaCaT Cells and Mouse Skin via CCDC25/MAPK Pathway","authors":"Yang Zou,&nbsp;Junzhi Li,&nbsp;Yuting Peng,&nbsp;Rui Hu,&nbsp;Ruolin Li,&nbsp;Aijun Chen","doi":"10.1111/acel.70640","DOIUrl":"10.1111/acel.70640","url":null,"abstract":"<p>The pathogenesis of skin photodamage remains incompletely elucidated. Neutrophil extracellular traps (NETs) have been implicated in exacerbating skin photodamage. However, their precise mechanism requires further investigation. We detected NETs via immunofluorescence in skin tissues from patients with Actinic Dermatosis. In vivo, an acute photodamage mouse model was established by using UVB irradiation. Mice were treated with GSK484 (PAD4 inhibitor) and subjected to RNA-sequencing to explore the mechanism by which NETs promote inflammation and apoptosis. NETs content, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were assessed. In vitro, immortalized keratinocytes (HaCaT cells) were treated with NETs. Subsequently, cell viability, reactive oxygen species (ROS) levels, inflammatory cytokine release, apoptosis, SOD production, and MDA levels were measured. 25-pass transmembrane protein (CCDC25) was knocked down to validate its role as a critical receptor for NETs in HaCaT cells. As a result, abundant NETs were present in the skin of Actinic Dermatosis patients. Injection of GSK484 significantly alleviated UVB-induced skin damage, inflammation, and cell apoptosis in the mouse model. RNA-sequencing analysis revealed that peptidyl-arginine deiminase 4 (PAD4) deficiency inhibited UVB-induced mitogen-activated protein kinase (MAPK) activation. NETs treatment induced HaCaT cell apoptosis, suppressed cell viability, promoted inflammatory cytokine release, and disrupted redox homeostasis. NETs stimulation increased phospho-Jun-N-terminal kinase (p-JNK) activity. However, this activity was suppressed and cellular status was restored following CCDC25 knockdown. Collectively, NETs exacerbate skin photodamage by activating the p-JNK/JNK pathway via CCDC25, leading to HaCaT cell apoptosis, inhibition of cell viability, and the release of inflammatory cytokines.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576149","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}