Aging Cell最新文献

{"title":"Regulation of Hsa-miR-4639-5p expression and its potential role in the pathogenesis of Parkinson's disease","authors":"Lu He,&nbsp;Yimeng Chen,&nbsp;Suzhen Lin,&nbsp;Ruinan Shen,&nbsp;Hong Pan,&nbsp;Yifan Zhou,&nbsp;Ying Wang,&nbsp;Shengdi Chen,&nbsp;Jianqing Ding","doi":"10.1111/acel.13840","DOIUrl":"https://doi.org/10.1111/acel.13840","url":null,"abstract":"<p>Decreased DJ-1 protein impairs antioxidative activity of neurons and plays an important role in the occurrence of Parkinson's disease (PD). We have previously identified hsa-miR-4639-5p as the post-transcriptional regulator of DJ-1. Increased expression of hsa-miR-4639-5p reduced DJ-1 level and increased oxidative stress leading to neuronal death. Therefore, understanding the detailed mechanisms by which hsa-miR-4639-5p expression is regulated will not only facilitate diagnosis but also inform the pathogenesis of PD. We examined hsa-miR-4639-5 in either the plasma or exosomes derived from the central nervous system (CNS) neurons of PD patients and healthy controls. We showed that CNS-derived exosomes gave rise to the increased plasma hsa-miR-4639-5p in PD patients, pointing to hsa-miR-4639-5p dysregulation in the brain of PD patients. Using a dual-luciferase assay and a CRISPR-Cas9 system, we identified a core promoter of hsa-miR-4639 (−560 to −275 upstream the transcriptional starting site) of the gene for myosin regulatory light chain interacting protein. A polymorphism in the core promoter (rs760632 G&gt;A) could enhance hsa-miR-4639-5p expression and increase PD risk. Furthermore, using MethylTarget™ assay, ChIP-qPCR, and specific inhibitors, we demonstrated that hsa-miR4639-5p expression was regulated by HDAC11-mediated histone acetylation but not DNA methylation/demethylation. Taken together, our study provides evidence that hsa-miR-4639-5p is a potential diagnostic marker and therapeutic target for PD. Interventions targeting hsa-miR-4639-5p might represent a novel therapy to promote healthy aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 6","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6046518","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":"Sexual dimorphism in the peripheral metabolic homeostasis and behavior in the TgF344-AD rat model of Alzheimer's disease","authors":"Hemant Srivastava,&nbsp;Alexander Tate Lasher,&nbsp;Akash Nagarajan,&nbsp;Liou Y. Sun","doi":"10.1111/acel.13854","DOIUrl":"https://doi.org/10.1111/acel.13854","url":null,"abstract":"<p>Alzheimer's disease (AD), a prevalent form of dementia, is characterized by the decline of cognitive abilities with age. Available treatment options for AD are limited, making it a significant public health concern. Recent research suggests that metabolic dysfunction plays a role in the development of AD. In addition, insulin therapy has been shown to improve memory in patients with cognitive decline. In this study, we report the first examination of body composition, peripheral insulin sensitivity, and glucose tolerance in relation to behavioral assessments of learning, memory, and anxiety in the TgF344-AD rat model of AD. Results from glucose and insulin tolerance tests show that female TgF344-AD rats exhibit impaired glucose clearance and reduced insulin sensitivity at both 9 and 12 months of age, while males display no differences at 9 months and even improved glucose clearance at 12 months. Results from the Morris Water Maze assessment of learning and memory reveal that male TgF344-AD rats display impairments at both 9 and 12 months of age, while female TgF344-AD rats only show impairments at 12 months. Furthermore, results from open field and elevated plus maze tests suggest that female TgF344-AD rats display increased anxiety at 9 months of age; however, no differences were detected in males or at 12 months of age. Overall, our findings suggest that impairments in metabolism, commonly associated with type 2 diabetes, occur before or simultaneously with cognitive decline and anxiety in a sexually dimorphic manner in the TgF344-AD rat model.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 7","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5784485","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":"Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice","authors":"Niraj Shrestha,&nbsp;Pallavi Chaturvedi,&nbsp;Xiaoyun Zhu,&nbsp;Michael J. Dee,&nbsp;Varghese George,&nbsp;Christopher Janney,&nbsp;Jack O. Egan,&nbsp;Bai Liu,&nbsp;Mark Foster,&nbsp;Lynne Marsala,&nbsp;Pamela Wong,&nbsp;Celia C. Cubitt,&nbsp;Jennifer A. Foltz,&nbsp;Jennifer Tran,&nbsp;Timothy Schappe,&nbsp;Karin Hsiao,&nbsp;Gilles M. Leclerc,&nbsp;Lijing You,&nbsp;Christian Echeverri,&nbsp;Catherine Spanoudis,&nbsp;Ana Carvalho,&nbsp;Leah Kanakaraj,&nbsp;Crystal Gilkes,&nbsp;Nicole Encalada,&nbsp;Lin Kong,&nbsp;Meng Wang,&nbsp;Byron Fang,&nbsp;Zheng Wang,&nbsp;Jin-an Jiao,&nbsp;Gabriela J. Muniz,&nbsp;Emily K. Jeng,&nbsp;Nicole Valdivieso,&nbsp;Liying Li,&nbsp;Richard Deth,&nbsp;Melissa M. Berrien-Elliott,&nbsp;Todd A. Fehniger,&nbsp;Peter R. Rhode,&nbsp;Hing C. Wong","doi":"10.1111/acel.13806","DOIUrl":"https://doi.org/10.1111/acel.13806","url":null,"abstract":"<p>Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic <i>db/db</i> mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro-inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single-nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell-cycle, and senescence-associated pathways in naturally aged mice. Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5866554","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":"Heterozygous OT-I mice reveal that antigen-specific CD8+ T cells shift from apoptotic to necrotic killers in the elderly","authors":"Dorina Z?phel,&nbsp;Lea Kaschek,&nbsp;Romy Steiner,&nbsp;Sandra Janku,&nbsp;Hsin-Fang Chang,&nbsp;Annette Lis","doi":"10.1111/acel.13824","DOIUrl":"https://doi.org/10.1111/acel.13824","url":null,"abstract":"<p>Numerous alterations in CD8⁺ T cells contribute to impaired immune responses in elderly individuals. However, the discrimination between cell-intrinsic dysfunctions and microenvironmental changes is challenging. TCR transgenic OT-I mice are utilized to investigate CD8⁺ T-cell immunity, but their immunodeficient phenotype hampers their use especially in aging. Here, we demonstrate that using a heterozygous OT-I model minimizes the current limitations and provides a valuable tool to assess antigen-specific T-cell responses even at old age. We analyzed phenotypic and functional characteristics of CD8⁺ T cells from OT-I^+/+ and OT-I^+/− mice to prove the applicability of the heterozygous system. Our data reveal that OVA-activated CD8⁺ T cells from adult OT-I^+/− mice proliferate, differentiate, and exert cytolytic activity equally to their homozygous counterparts. Moreover, common age-related alterations in CD8⁺ T cells, including naive T-cell deterioration and decreased proliferative capacity, also occur in elderly OT-I^+/− mice, indicating the wide range of applications for in vivo and in vitro aging studies. We used the OT-I^+/− model to investigate cell-intrinsic alterations affecting the cytotoxic behavior of aged CD8⁺ T cells after antigen-specific in vitro activation. Time-resolved analysis of antigen-directed target cell lysis confirmed previous observations that the cytotoxic capacity of CD8⁺ T cells increases with age. Surprisingly, detailed single cell analysis revealed that transcriptional upregulation of perforin in aged CD8⁺ T cells shifts the mode of target cell death from granzyme-mediated apoptosis to rapid induction of necrosis. This unexpected capability might be beneficial or detrimental for the aging host and requires detailed evaluation.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 6","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5670963","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":"Glucagon-like peptide-1 receptor agonists to expand the healthy lifespan: Current and future potentials","authors":"Frederik Flindt Kreiner,&nbsp;Bernt Johan von?Scholten,&nbsp;Peter Kurtzhals,&nbsp;Stephen Charles Langford Gough","doi":"10.1111/acel.13818","DOIUrl":"https://doi.org/10.1111/acel.13818","url":null,"abstract":"<p>To help ensure an expanded healthy lifespan for as many people as possible worldwide, there is a need to prevent or manage a number of prevalent chronic diseases directly and indirectly closely related to aging, including diabetes and obesity. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have proven beneficial in type 2 diabetes, are amongst the few medicines approved for weight management, and are also licensed for focused cardiovascular risk reduction. In addition, strong evidence suggests several other beneficial effects of the pleiotropic peptide hormone, including anti-inflammation. Consequently, GLP-1 RAs are now in advanced clinical development for the treatment of chronic kidney disease, broader cardiovascular risk reduction, metabolic liver disease and Alzheimer's disease. In sum, GLP-1 RAs are positioned as one of the pharmacotherapeutic options that can contribute to addressing the high unmet medical need characterising several prevalent aging-related diseases, potentially helping more people enjoy a prolonged healthy lifespan.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5951347","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":"Large-Scale metabolomics: Predicting biological age using 10,133 routine untargeted LC–MS measurements","authors":"Johan K. Lassen,&nbsp;Tingting Wang,&nbsp;Kirstine L. Nielsen,&nbsp;J?rgen B. Hasselstr?m,&nbsp;Mogens Johannsen,&nbsp;Palle Villesen","doi":"10.1111/acel.13813","DOIUrl":"https://doi.org/10.1111/acel.13813","url":null,"abstract":"<p>Untargeted metabolomics is the study of all detectable small molecules, and in geroscience, metabolomics has shown great potential to describe the biological age—a complex trait impacted by many factors. Unfortunately, the sample sizes are often insufficient to achieve sufficient power and minimize potential biases caused by, for example, demographic factors. In this study, we present the analysis of biological age in ~10,000 toxicologic routine blood measurements. The untargeted screening samples obtained from ultra-high pressure liquid chromatography-quadruple time of flight mass spectrometry (UHPLC- QTOF) cover + 300 batches and + 30 months, lack pooled quality controls, lack controlled sample collection, and has previously only been used in small-scale studies. To overcome experimental effects, we developed and tested a custom neural network model and compared it with existing prediction methods. Overall, the neural network was able to predict the chronological age with an rmse of 5.88 years (<i>r</i>^<i>2</i> = 0.63) improving upon the 6.15 years achieved by existing normalization methods. We used the feature importance algorithm, Shapley Additive exPlanations (SHAP), to identify compounds related to the biological age. Most importantly, the model returned known aging markers such as kynurenine, indole-3-aldehyde, and acylcarnitines along with a potential novel aging marker, cyclo (leu-pro). Our results validate the association of tryptophan and acylcarnitine metabolism to aging in a highly uncontrolled large-s cale sample. Also, we have shown that by using robust computational methods it is possible to deploy large LC-MS datasets for metabolomics studies to reduce the risk of bias and empower aging studies.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5730977","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":"Measuring biological age using a functionally interpretable multi-tissue RNA clock","authors":"Sascha Jung,&nbsp;Javier Arcos?Hodar,&nbsp;Antonio del?Sol","doi":"10.1111/acel.13799","DOIUrl":"https://doi.org/10.1111/acel.13799","url":null,"abstract":"<p>The quantification of the biological age of cells yields great promises for accelerating the discovery of novel rejuvenation strategies. Here, we present MultiTIMER, the first multi-tissue aging clock that measures the biological, rather than chronological, age of cells from their transcriptional profiles by evaluating key cellular processes. We applied MultiTIMER to more than 70,000 transcriptional profiles and demonstrate that it accurately responds to cellular stressors and known interventions while informing about dysregulated cellular functions.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5673705","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":"Enhanced insulin-regulated phagocytic activities support extreme health span and longevity in multiple populations","authors":"Deng Wu,&nbsp;Xiaoman Bi,&nbsp;Peihu Li,&nbsp;Dahua Xu,&nbsp;Jianmin Qiu,&nbsp;Kongning Li,&nbsp;Shaojiang Zheng,&nbsp;Kim Hei-Man Chow","doi":"10.1111/acel.13810","DOIUrl":"https://doi.org/10.1111/acel.13810","url":null,"abstract":"<p>The immune system plays a central role in many processes of age-related disorders and it remains unclear if the innate immune system may play roles in shaping extreme longevity. By an integrated analysis with multiple bulk and single cell transcriptomic, so as DNA methylomic datasets of white blood cells, a previously unappreciated yet commonly activated status of the innate monocyte phagocytic activities is identified. Detailed analyses revealed that the life cycle of these monocytes is enhanced and primed to a M2-like macrophage phenotype. Functional characterization unexpectedly revealed an insulin-driven immunometabolic network which supports multiple aspects of phagocytosis. Such reprogramming is associated to a skewed trend of DNA demethylation at the promoter regions of multiple phagocytic genes, so as a direct transcriptional effect induced by nuclear-localized insulin receptor. Together, these highlighted that preservation of insulin sensitivity is a key to healthy lifespan and extended longevity, via boosting the function of innate immune system in advanced ages.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6154298","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":"Ensheathing glia promote increased lifespan and healthy brain aging","authors":"Lihong Sheng,&nbsp;Emily J. Shields,&nbsp;Janko Gospocic,&nbsp;Masato Sorida,&nbsp;Linyang Ju,&nbsp;China N. Byrns,&nbsp;Faith Carranza,&nbsp;Shelley L. Berger,&nbsp;Nancy Bonini,&nbsp;Roberto Bonasio","doi":"10.1111/acel.13803","DOIUrl":"https://doi.org/10.1111/acel.13803","url":null,"abstract":"<p>Glia have an emergent role in brain aging and disease. In the <i>Drosophila melanogaster</i> brain, ensheathing glia function as phagocytic cells and respond to acute neuronal damage, analogous to mammalian microglia. We previously reported changes in glia composition over the life of ants and fruit flies, including a decline in the relative proportion of ensheathing glia with time. How these changes influence brain health and life expectancy is unknown. Here, we show that ensheathing glia but not astrocytes decrease in number during <i>Drosophila melanogaster</i> brain aging. The remaining ensheathing glia display dysregulated expression of genes involved in lipid metabolism and apoptosis, which may lead to lipid droplet accumulation, cellular dysfunction, and death. Inhibition of apoptosis rescued the decline of ensheathing glia with age, improved the neuromotor performance of aged flies, and extended lifespan. Furthermore, an expanded ensheathing glia population prevented amyloid-beta accumulation in a fly model of Alzheimer's disease and delayed the premature death of the diseased animals. These findings suggest that ensheathing glia play a vital role in regulating brain health and animal longevity.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5787831","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":"Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging","authors":"Cui Zhu,&nbsp;Duilio M. Potenza,&nbsp;Yang Yang,&nbsp;Guillaume Ajalbert,&nbsp;Kirsten D. Mertz,&nbsp;Stephan von Gunten,&nbsp;Xiu-Fen Ming,&nbsp;Zhihong Yang","doi":"10.1111/acel.13790","DOIUrl":"https://doi.org/10.1111/acel.13790","url":null,"abstract":"<p>Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in <i>arg-ii</i> deficient (<i>arg-ii</i>^{<i>−/−</i>}) mice. The effects of <i>arg-ii</i>^{<i>−</i>/−} on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from <i>arg-ii</i>^{<i>−/−</i>} cells, activates fibroblasts to produce various cytokines including TGF-β1 and collagen, which is abolished by IL-1β receptor antagonist or TGF-β type I receptor blocker. Conversely, TGF-β1 or IL-1β also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1β and TGF-β1 in epithelial cells and activation of fibroblasts, which is inhibited in <i>arg-ii</i>^{<i>−</i>/−} mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1β and TGF-β1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5651727","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}