Aging Cell最新文献_第7页

Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice 间歇性禁食通过髓磷脂保存增强老年小鼠的运动协调能力。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14476

Zhuang Liu, Ziyue Zhao, Hongying Du, Qingqing Zhou, Mei Li, Zhu Gui, Jinfeng Wu, Yunling Gao, Ning Zheng, Yu Zhang, Ailian Du, Hongxing Wang, Jie Wang

{"title":"Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice","authors":"Zhuang Liu, Ziyue Zhao, Hongying Du, Qingqing Zhou, Mei Li, Zhu Gui, Jinfeng Wu, Yunling Gao, Ning Zheng, Yu Zhang, Ailian Du, Hongxing Wang, Jie Wang","doi":"10.1111/acel.14476","DOIUrl":"10.1111/acel.14476","url":null,"abstract":"Integrating dietary interventions have been extensively studied for their health benefits, such as Alzheimer's disease, Huntington's disease, and aging. However, it is necessary to fully understand the mechanisms of long-term effects and practical applications of these dietary interventions for health. A 10-week intermittent fasting (IMF) regimen was implemented on the aging animals in the current study. The variations of cerebral functions were analyzed employing a comprehensive experimental design that includes behavioral tests, neuroimaging, and ultrastructural analysis, such as resting-state functional MRI (rsfMRI), EEG/EMG recordings, transmission electron microscopy, and immunohistochemistry. Over a 10-week regimen, IMF significantly improved locomotor activity, motor coordination, and muscle strength compared to controls (p < 0.01). Resting-state fMRI (rsfMRI) demonstrated that IMF modulates brain-wide functional connectivity, enhancing communication between key brain regions. Advanced imaging techniques revealed increased expression of myelin-related proteins, including myelin basic protein (MBP), and myelin-associated glycoprotein (MAG), indicating enhanced myelin integrity and repair, particularly in axons with diameters < 400 nm (p < 0.01). These findings suggest that IMF may mitigate age-related declines by promoting better neuronal signaling. This study highlights the potential function of IMF as a non-pharmacological intervention to promote brain health and mitigate cognitive decline in aging populations.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941605","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}

引用次数: 0

Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling 膳食肉桂通过mTORC1和自噬信号促进长寿和延长健康寿命。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-06 DOI: 10.1111/acel.14448

Yuling Guo, Qing Zhang, Bi Zhang, Tong Pan, Elizabeth A. Ronan, Anthony Huffman, Yongqun He, Ken Inoki, Jianfeng Liu, X.Z. Shawn Xu

{"title":"Dietary cinnamon promotes longevity and extends healthspan via mTORC1 and autophagy signaling","authors":"Yuling Guo, Qing Zhang, Bi Zhang, Tong Pan, Elizabeth A. Ronan, Anthony Huffman, Yongqun He, Ken Inoki, Jianfeng Liu, X.Z. Shawn Xu","doi":"10.1111/acel.14448","DOIUrl":"10.1111/acel.14448","url":null,"abstract":"Cinnamon, renowned for its aromatic flavor, represents one of the most widely used spices worldwide. Cinnamon is also considered beneficial to human health with therapeutic potential for treating various diseases, ranging from diabetes and cancer to neurodegenerative diseases. However, the mechanisms underlying cinnamon's health benefits remain elusive. It is also unclear whether cinnamon has any role in aging. Using C. elegans as a model, here we show that feeding worms cinnamaldehyde (CA), the active ingredient in cinnamon oil, prolongs longevity. CA also promotes stress resistance and reduces β-Amyloid toxicity in a C. elegans model of Alzheimer's disease. Mechanistically, CA exerts its beneficial effects through mTORC1 and autophagy signaling. Interestingly, CA promotes longevity by inducing a dietary restriction-like state without affecting food intake, suggesting CA as a dietary restriction mimetic. In human cells, CA exerts a similar effect on mTORC1 and autophagy signaling, suggesting a conserved mechanism. Our results demonstrate that dietary cinnamon promotes both lifespan and healthspan and does so by regulating mTORC1 and autophagy signaling.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929994","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}

引用次数: 0

Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation 衰老相关的isoDGR基序在慢性肺部炎症中的免疫治疗靶向。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-05 DOI: 10.1111/acel.14425

Pazhanichamy Kalailingam, SoFong Cam Ngan, Ranjith Iyappan, Afra Nehchiri, Khalilatul-Hanisah Mohd-Kahliab, Benjamin Sian Teck Lee, Bhargy Sharma, Radek Machan, Sint Thida Bo, Emma S. Chambers, Val A. Fajardo, Rebecca E. K. Macpherson, Jian Liu, Panagiota Klentrou, Evangelia Litsa Tsiani, Kah Leong Lim, I. Hsin Su, Yong-Gui Gao, A. Mark Richar, Raj N. Kalaria, Christopher P. Chen, Cynthia Balion, Dominique de Kleijn, Neil E. McCarthy, Siu Kwan Sze

{"title":"Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation","authors":"Pazhanichamy Kalailingam, SoFong Cam Ngan, Ranjith Iyappan, Afra Nehchiri, Khalilatul-Hanisah Mohd-Kahliab, Benjamin Sian Teck Lee, Bhargy Sharma, Radek Machan, Sint Thida Bo, Emma S. Chambers, Val A. Fajardo, Rebecca E. K. Macpherson, Jian Liu, Panagiota Klentrou, Evangelia Litsa Tsiani, Kah Leong Lim, I. Hsin Su, Yong-Gui Gao, A. Mark Richar, Raj N. Kalaria, Christopher P. Chen, Cynthia Balion, Dominique de Kleijn, Neil E. McCarthy, Siu Kwan Sze","doi":"10.1111/acel.14425","DOIUrl":"10.1111/acel.14425","url":null,"abstract":"Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation. We observed age-dependent accumulation of the isoDGR motif in human lung tissues, as well as an 8-fold increase in isoDGR-damaged proteins in lung fibrotic tissues compared with healthy tissue. This increase was accompanied by marked infiltration of CD68+/CD11b + macrophages, consistent with a role for isoDGR in promoting chronic inflammation. We therefore assessed isoDGR function in mice that were either naturally aged or lacked the isoDGR repair enzyme. IsoDGR-protein accumulation in mouse lung tissue was strongly correlated with chronic inflammation, pulmonary edema, and hypoxemia. This accumulation also induced mitochondrial and ribosomal dysfunction, in addition to features of cellular senescence, thereby contributing to progressive lung damage over time. Importantly, treatment with anti-isoDGR antibody was able to reduce these molecular features of disease and significantly reduced lung pathology in vivo.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930006","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}

引用次数: 0

DeepQA: A Unified Transcriptome-Based Aging Clock Using Deep Neural Networks DeepQA：使用深度神经网络的统一转录组老化时钟。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-05 DOI: 10.1111/acel.14471

Hongqian Qi, Hongchen Zhao, Enyi Li, Xinyi Lu, Ningbo Yu, Jinchao Liu, Jianda Han

{"title":"DeepQA: A Unified Transcriptome-Based Aging Clock Using Deep Neural Networks","authors":"Hongqian Qi, Hongchen Zhao, Enyi Li, Xinyi Lu, Ningbo Yu, Jinchao Liu, Jianda Han","doi":"10.1111/acel.14471","DOIUrl":"10.1111/acel.14471","url":null,"abstract":"Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on both healthy and unhealthy subjects. However, the inherent bias in this approach results in inaccurate biological age as shown in this study. Moreover, almost all existing transcriptome-based aging clocks were built around an inefficient procedure of gene selection followed by conventional machine learning models such as elastic nets, linear discriminant analysis etc. To address these limitations, we proposed DeepQA, a unified aging clock based on mixture of experts. Unlike existing methods, DeepQA is equipped with a specially designed Hinge-Mean-Absolute-Error (Hinge-MAE) loss so that it can train on both healthy and unhealthy subjects of multiple cohorts to reduce the bias of inferring biological age of unhealthy subjects. Our experiments showed that DeepQA significantly outperformed existing methods for biological age estimation on both healthy and unhealthy subjects. In addition, our method avoids the inefficient exhaustive search of genes, and provides a novel means to identify genes activated in aging prediction, alternative to such as differential gene expression analysis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929991","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}

引用次数: 0

Differential Organ Ageing Is Associated With Age-Related Macular Degeneration 不同器官老化与年龄相关性黄斑变性有关。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-05 DOI: 10.1111/acel.14473

Anastasios Papadam, Arimantas Lionikas, Felix Grassmann

{"title":"Differential Organ Ageing Is Associated With Age-Related Macular Degeneration","authors":"Anastasios Papadam, Arimantas Lionikas, Felix Grassmann","doi":"10.1111/acel.14473","DOIUrl":"10.1111/acel.14473","url":null,"abstract":"Age-related macular degeneration (AMD) is a progressive disorder and the leading cause of central vision loss. Age is the most important risk factor, followed by genetics and smoking. However, ageing is a complex process, and biological age can deviate from chronological age between individuals and within different organ systems. Initially, we used machine learning to predict the biological age of the immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic and hepatic systems by analysing various physiological and physical markers in the UK Biobank cohort. Then, we investigated the association of each organ's biological age with incident AMD derived from electronic health record data as well as with different AMD genetic risk scores. We observed that most organ systems in participants who developed AMD after recruitment showed accelerated ageing compared with controls, with the immune system being the most affected, especially in younger males. Surprisingly, we found that AMD patients showed slower ageing of their hepatic system compared to controls, particularly in female patients. The overall AMD genetic risk score was associated with faster organ ageing across all tissues except cardiovascular and pulmonary, while genetic risk scores stratified by pathways differently influenced each organ system. In conclusion, we found differential organ ageing associated with AMD. Significantly, genetic risk variants of AMD are associated with differential ageing of various organ systems.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930000","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}

引用次数: 0

Elevated p16Ink4a Expression Enhances Tau Phosphorylation in Neurons Differentiated From Human-Induced Pluripotent Stem Cells p16Ink4a表达升高可增强人诱导多能干细胞分化神经元的Tau磷酸化

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-05 DOI: 10.1111/acel.14472

Kristopher Holloway, Kashfia Neherin, Yingduo Song, Kazuhito Sato, Andrew Houston, Feng Chen, Li Ding, Hong Zhang

{"title":"Elevated p16Ink4a Expression Enhances Tau Phosphorylation in Neurons Differentiated From Human-Induced Pluripotent Stem Cells","authors":"Kristopher Holloway, Kashfia Neherin, Yingduo Song, Kazuhito Sato, Andrew Houston, Feng Chen, Li Ding, Hong Zhang","doi":"10.1111/acel.14472","DOIUrl":"10.1111/acel.14472","url":null,"abstract":"Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a doxycycline-inducible system to trigger p16 up-regulation in human-induced pluripotent stem cells (iPSCs) and neurons differentiated from iPSCs. We demonstrated that up-regulated p16 expression in iPSCs reduces cell proliferation, down-regulates cell cycle genes, and up-regulates genes involved in focal adhesion, interferon α response and PI3K-Akt signaling. Our approach enables temporal control of p16 induction upon differentiation from iPSCs to neurons. In differentiated cortical neurons, we found that up-regulation of p16 increases tau phosphorylation at Ser202/Thr205 and Thr231 in a cell-autonomous manner, while amyloid beta secretion is not affected. These data suggest a critical role of p16 in regulating tau phosphorylation in neurons, and thereby contributing to pathological progression of AD. As pathological tau tangles have been shown to induce p16 expression, our studies suggest a positive feedback loop between p16 and tau to exacerbate tau pathologies.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930002","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}

引用次数: 0

Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate Efferocytosis：衰老和肿瘤命运的双面守门人。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-03 DOI: 10.1111/acel.14467

Zaoqu Liu, Yan Li, Yuqing Ren, Jingqi Chen, Siyuan Weng, Zhaokai Zhou, Peng Luo, Quan Chen, Hui Xu, Yuhao Ba, Anning Zuo, Shutong Liu, Yuyuan Zhang, Teng Pan, Xinwei Han

{"title":"Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate","authors":"Zaoqu Liu, Yan Li, Yuqing Ren, Jingqi Chen, Siyuan Weng, Zhaokai Zhou, Peng Luo, Quan Chen, Hui Xu, Yuhao Ba, Anning Zuo, Shutong Liu, Yuyuan Zhang, Teng Pan, Xinwei Han","doi":"10.1111/acel.14467","DOIUrl":"10.1111/acel.14467","url":null,"abstract":"From embryogenesis to aging, billions of cells perish daily in mammals. The multistep process by which phagocytes engulf these deceased cells without eliciting an inflammatory response is called efferocytosis. Despite significant insights into the fundamental mechanisms of efferocytosis, its implications in disorders such as aging and cancer remain elusive. Upon summarizing and analyzing existing studies on efferocytosis, it becomes evident that efferocytosis is our friend in resolving inflammation, yet it transforms into our foe by facilitating tumor development and metastasis. This review illuminates recent discoveries regarding the emerging mechanisms of efferocytosis in clearing apoptotic cells, explores its connections with aging, examines its influence on tumor development and metastasis, and identifies the regulatory factors of efferocytosis within the tumor microenvironment. A comprehensive understanding of these efferocytosis facets offers insights into crucial physiological and pathophysiological processes, paving the way for innovative therapeutic approaches to combat aging and cancer.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918678","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}

引用次数: 0

Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia tgm2催化的i -κB α共价交联驱动NF-κB核易位促进衰老小胶质细胞SASP。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-03 DOI: 10.1111/acel.14463

Zhiqiang Li, Tianxiang Wang, Sijing Du, Zelong Miao, Yujiao Zhao, Yuxiang Tang, Xianbin Meng, Shangcheng Yu, Dongyuan Zhang, Hao Jiang, Kunlin Du, Wei Wei, Haiteng Deng

{"title":"Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia","authors":"Zhiqiang Li, Tianxiang Wang, Sijing Du, Zelong Miao, Yujiao Zhao, Yuxiang Tang, Xianbin Meng, Shangcheng Yu, Dongyuan Zhang, Hao Jiang, Kunlin Du, Wei Wei, Haiteng Deng","doi":"10.1111/acel.14463","DOIUrl":"10.1111/acel.14463","url":null,"abstract":"Microglia, as resident immune cells in the central nervous system (CNS), play a crucial role in maintaining homeostasis and phagocytosing metabolic waste in the brain. Senescent microglia exhibit decreased phagocytic capacity and increased neuroinflammation through senescence-associated secretory phenotype (SASP). This process contributes to the development of various neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we found that SASP was elevated in senescent microglia, and proteomics showed that Tgm2 was upregulated. Mechanistically, we revealed that Tgm2-catalyzed covalent cross-linking of IκBα at K22 and Q248 residues in the cytoplasm of microglia, resulting in the reduction of IκBα and nuclear translocation of NF-κB to promote SASP production. Treatment of senescent microglia with Tgm2 inhibitors (Tg2-IN1 and Cys-D) resulted in reduced NF-κB nuclear translocation and decreased SASP. Additionally, oral administration of Cys-D significantly improved the aging phenotype in aged mice. To summarize, Tgm2 is a potential target for antiaging, and inhibitors of Tgm2 can serve as novel prophylactics or senomorphics.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918682","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}

引用次数: 0

Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice 在老年小鼠中，抗衰老治疗减少免疫细胞浸润，但不改善IAV结果。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-03 DOI: 10.1111/acel.14437

Adrian Luna, Kai-Neng Chou, Kathleen M. Wragg, Matthew J. Worley, Nikhil Paruchuri, Xiaofeng Zhou, Muriel G. Blin, Bethany B. Moore, Morgan Salmon, Daniel R. Goldstein, Jane C. Deng

{"title":"Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice","authors":"Adrian Luna, Kai-Neng Chou, Kathleen M. Wragg, Matthew J. Worley, Nikhil Paruchuri, Xiaofeng Zhou, Muriel G. Blin, Bethany B. Moore, Morgan Salmon, Daniel R. Goldstein, Jane C. Deng","doi":"10.1111/acel.14437","DOIUrl":"10.1111/acel.14437","url":null,"abstract":"Aging is a major risk factor for poor outcomes following respiratory infections. In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced lung damage and increased survival, little is known about the role that senescent cells play in the outcome of influenza A viral (IAV) infections in aged mice. Here, we tested if the aged mice survival or weight loss IAV infections could be improved using three different senolytic regimens. We found that neither dasatinib plus quercetin, fisetin, nor ABT-263 improved outcomes. Furthermore, both dasatanib plus quercetin and fisetin treatments further suppressed immune infiltration than aging alone. Additionally, our data show that the short-term senolytic agents do not reduce senescent markers in our aged mouse model. These findings suggest that acute senolytic treatments do not universally reverse aging related immune phenotype against all respiratory viral infections.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925910","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}

引用次数: 0

circSIRT2/miR-542-3p/VASH1 axis regulates endothelial-to-mesenchymal transition (EndMT) in subretinal fibrosis in age-related macular degeneration models circSIRT2/miR-542-3p/VASH1轴调节年龄相关性黄斑变性模型中视网膜下纤维化的内皮到间质转化（EndMT）。

IF 7.8 1区医学

Aging Cell Pub Date : 2025-01-02 DOI: 10.1111/acel.14443

Min Zhang, Jiali Wu, Yimin Wang, Yidong Wu, Xiaoling Wan, Mei Jiang, Qiyu Bo, Jieqiong Chen, Xiaodong Sun

{"title":"circSIRT2/miR-542-3p/VASH1 axis regulates endothelial-to-mesenchymal transition (EndMT) in subretinal fibrosis in age-related macular degeneration models","authors":"Min Zhang, Jiali Wu, Yimin Wang, Yidong Wu, Xiaoling Wan, Mei Jiang, Qiyu Bo, Jieqiong Chen, Xiaodong Sun","doi":"10.1111/acel.14443","DOIUrl":"10.1111/acel.14443","url":null,"abstract":"Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is one of the leading causes of severe visual impairment and irreversible vision loss around the world. Subretinal fibrosis (SRF) contributes to the incomplete response to anti-vascular endothelial growth factor (VEGF) treatment and is one of the main reasons for long-term poor visual outcomes in nAMD. Reducing SRF is urgently needed in the anti-VEGF era. The role of non-coding RNAs has been implicated in CNV; however, their roles in SRF have not been elucidated yet. Herein, we comprehensively investigated circular RNA (circRNA) profiles in the laser-induced mouse SRF model and the transforming growth factor-β (TGF-β) induced human umbilical vein endothelial cell (HUVEC) fibrosis model. A novel circRNA, circSIRT2, was identified, and its function in SRF and endothelial-to-mesenchymal transition (EndMT) regulation was investigated. circSIRT2 was consistently upregulated in fibrotic models in vivo and in vitro. circSIRT2 overexpression downregulated the fibrotic markers and inhibited the proliferation and migration of endothelial cells in vitro. circSIRT2 overexpression in vivo also reduced SRF area in mice. Mechanistically, circSIRT2 functioned by sponging miR-542-3p, which further upregulated the expression of vasohibin-1 (VASH1) and reduced SRF lesion development. Vitreous delivery of miR-542-3p and VASH1 in the mouse SRF model also confirmed the pro-fibrotic function of miR-542-3p and anti-fibrotic function of VASH1, respectively. In conclusion, circSIRT2 inhibited SRF by binding miR-542-3p, which stimulated the VASH1 expression and subsequently suppressed EndMT. The circSIRT2/miR-542-3p/VASH1 axis may serve as a promising therapeutic target for SRF in nAMD.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913432","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}

引用次数: 0