Aging Cell最新文献_第6页

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 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":"https://doi.org/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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14473"},"PeriodicalIF":8.0,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14472"},"PeriodicalIF":8.0,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":"https://doi.org/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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14463"},"PeriodicalIF":8.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14437"},"PeriodicalIF":8.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":"https://doi.org/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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14443"},"PeriodicalIF":8.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the Role of TRPV4 and GPR35 Interaction in Endothelial Dysfunction in Aging Mice. 研究TRPV4和GPR35相互作用在衰老小鼠内皮功能障碍中的作用。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-02 DOI: 10.1111/acel.14469

Xiaoxue Tian, Hao Kan, Liu Yang, Zhiwei Wang, Tiantian Zhang, Ka Zhang, Aiqin Mao, Xin Wen, Tingting Zhou, Xiaoyan Wang, Xiaodong Zhang, Lei Feng, Li Geng

{"title":"Investigating the Role of TRPV4 and GPR35 Interaction in Endothelial Dysfunction in Aging Mice.","authors":"Xiaoxue Tian, Hao Kan, Liu Yang, Zhiwei Wang, Tiantian Zhang, Ka Zhang, Aiqin Mao, Xin Wen, Tingting Zhou, Xiaoyan Wang, Xiaodong Zhang, Lei Feng, Li Geng","doi":"10.1111/acel.14469","DOIUrl":"https://doi.org/10.1111/acel.14469","url":null,"abstract":"Endothelial dysfunction, characterized by a decline in endothelial physiological functions, is a significant aspect of cardiovascular aging, contributing notably to arterial stiffness, atherosclerosis, and hypertension. Transient receptor potential channel V4 (TRPV4), a key member of Ca2+-permeable channels, plays a crucial role in maintaining vascular functions. However, the role and mechanisms of TRPV4 in aging-related endothelial dysfunction remain incompletely understood. Here, we demonstrated a marked reduction in endothelial TRPV4 function without alterations in its expression, leading to abnormal endothelial Ca2+ signaling and impaired vasodilation in aging mesenteric arteries. Employing transcriptome sequencing, co-IP, and PLA assays, we characterized G protein-coupled receptor 35 (GPR35) interacting with TRPV4, and abnormally enhanced interactions were found in aging endothelial cells. Subsequently, we revealed that intensive GPR35-TRPV4 interaction significantly contributes to endothelial dysfunction during aging, utilizing TRPV4 endothelial-specific knockout (TRPV4EC -/-), AAV-FLT1-shRNA (GPR35) mice, and GPR35 overexpressed/knocked-down HUVECs. Furthermore, molecular docking analysis and subsequent co-IP and pressure myograph experiments indicated that both Thonningianin A and Carfilzomib efficiently restored the GPR35-TRPV4 interaction, preventing endothelial dysfunction and vasodilation impairment. Our study identifies the crucial role of GPR35-TRPV4 interaction in aging-associated abnormal endothelial function and vascular tone modulation. Restoring GPR35-TRPV4 interaction via Thonningianin A or Carfilzomib represents a promising precision approach for aging-related endothelial dysfunction.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14469"},"PeriodicalIF":8.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 8 1区医学

Aging Cell Pub Date : 2025-01-02 DOI: 10.1111/acel.14460

Mingyan Fang, Yu Miao, Lin Zhu, Yunpeng Mei, Hui Zeng, Lihua Luo, Yuan Ding, Lina Zhou, Xueping Quan, Qin Zhao, Xiaodong Zhao, Yunfei An

{"title":"Age-Related Dynamics and Spectral Characteristics of the TCRβ Repertoire in Healthy Children: Implications for Immune Aging.","authors":"Mingyan Fang, Yu Miao, Lin Zhu, Yunpeng Mei, Hui Zeng, Lihua Luo, Yuan Ding, Lina Zhou, Xueping Quan, Qin Zhao, Xiaodong Zhao, Yunfei An","doi":"10.1111/acel.14460","DOIUrl":"https://doi.org/10.1111/acel.14460","url":null,"abstract":"T-cell receptor (TCR) diversity is crucial for adaptive immunity, yet baseline characterizations in pediatric populations remain sparse. We sequenced the TCRβ chain of 325 healthy Chinese children aged 0-18, categorized into six age groups. We also analyzed cellular composition and TCRβ associations using flow cytometry in 81 of these samples. Our results indicate a decrease in TCRβ diversity with age, characterized by an increase in high-frequency clonotypes and notable changes in CDR3 length and V(D)J gene usage. These changes are influenced by early life vaccinations and antigen exposures. Additionally, we found a significant association between reduced TCRβ diversity and a decrease in CD4+ T naïve cells. We also developed a predictive model that identifies specific TCRβ features as potential biomarkers for biological age, validated by their significant correlation with changes in the immune repertoire. These findings enhance our understanding of age-related variations in the TCRβ repertoire among children, providing resourceful information for research on pediatric TCR in health and disease.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14460"},"PeriodicalIF":8.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CALB1 and RPL23 Are Essential for Maintaining Oocyte Quality and Function During Aging. CALB1和RPL23对维持衰老过程中卵母细胞的质量和功能至关重要。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-02 DOI: 10.1111/acel.14466

Yingxue Han, Zihuan Du, Hao Wu, Rong Zhao, Jikang Liu, Shuai Gao, Shenming Zeng

{"title":"CALB1 and RPL23 Are Essential for Maintaining Oocyte Quality and Function During Aging.","authors":"Yingxue Han, Zihuan Du, Hao Wu, Rong Zhao, Jikang Liu, Shuai Gao, Shenming Zeng","doi":"10.1111/acel.14466","DOIUrl":"https://doi.org/10.1111/acel.14466","url":null,"abstract":"With advancing age, significant changes occur in the female reproductive system, the most notable of which is the decline in oocyte quality, a key factor affecting female fertility. However, the mechanisms underlying oocyte aging remain poorly understood. In this study, we obtained oocytes from aged and young female mice and performed single-cell transcriptome sequencing, comparing our findings with existing proteomic analyses. Our analysis revealed that one of the primary characteristics of aging oocytes is the disruption of calcium ion homeostasis. Specifically, we identified two key genes involved in the oocyte aging process, Calb1 and Rpl23. Experimental validation demonstrated that knockdown of CALB1 in oocytes led to reduced calcium ion levels in the endoplasmic reticulum and mitochondria, resulting in mitochondrial dysfunction and meiotic defects. Further experiments suggested that RPL23 may function as a downstream gene of CALB1, and its knockdown caused mitochondrial dysfunction, excessive accumulation of reactive oxygen species (ROS), and spindle assembly defects. Notably, overexpression of these two genes in aging oocytes partially rescued the maternal age-related defective phenotypes, underscoring their crucial roles in oocyte aging. This study provides a comprehensive understanding of the specific mechanisms underlying mouse oocyte aging at single-cell resolution, supported by experimental validation, and offers new directions and potential targets for future research into age-related reproductive health issues.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14466"},"PeriodicalIF":8.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying ENO1 as a protein target of chlorogenic acid to inhibit cellular senescence and prevent skin photoaging in mice. 确定ENO1作为绿原酸抑制细胞衰老和防止小鼠皮肤光老化的蛋白靶点。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-31 DOI: 10.1111/acel.14433

Xueling He, Chen Wang, Qianyu Zhang, Tong Yang, Qiuyan Guo, Yaxu Wang, Jiayue Guo, Pengjie Wang, Junzhe Zhang, Huan Tang, Yinhua Zhu, Jigang Wang

{"title":"Identifying ENO1 as a protein target of chlorogenic acid to inhibit cellular senescence and prevent skin photoaging in mice.","authors":"Xueling He, Chen Wang, Qianyu Zhang, Tong Yang, Qiuyan Guo, Yaxu Wang, Jiayue Guo, Pengjie Wang, Junzhe Zhang, Huan Tang, Yinhua Zhu, Jigang Wang","doi":"10.1111/acel.14433","DOIUrl":"https://doi.org/10.1111/acel.14433","url":null,"abstract":"Cellular senescence plays a critical role in repeated ultraviolet (UV) exposure-induced skin photoaging. Currently, from the perspective of regulating senescent cells, potent compounds or reliable protein targets that could effectively prevent skin photoaging have not yet been reported. Herein, we demonstrated that chlorogenic acid (CGA) significantly inhibited UVA-induced senescence of human dermis skin fibroblasts (HDF) cells by screening the natural product library. The activity-based protein profiling (ABPP) result revealed that Enolase 1 (ENO1) is one of the direct targets of CGA in HDF cells. Further mechanism research indicated that CGA covalently binds to ENO1, and prevented UVA-induced cellular senescence by suppressing the activity of ENO1 protein to block the glycolytic pathway. Importantly, we found that CGA dose-dependently reduced the skin wrinkle score, alleviated skin pathological features and inhibited senescent characteristics in a photoaging mouse model. The proteomic analysis revealed that CGA treatment effectively inhibited senescence-associated secretory phenotype (SASP) secretion and glycolysis in skin samples of mice. Collectively, our study not only demonstrated that inhibiting cell senescence is an effective anti-skin photoaging strategy, but also revealed that ENO1 is a promising protein target to prevent photoaging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14433"},"PeriodicalIF":8.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

P2Y₂ Inhibition Modifies the Anabolic Response to Exercise in Adult Mice. P2Y2抑制改变成年小鼠对运动的合成代谢反应。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-31 DOI: 10.1111/acel.14464

Amit Chougule, Chunbin Zhang, Jordan Denbow, Nickolas Vinokurov, Devin Mendez, Elizabeth Vojtisek, Joseph Gardinier

{"title":"P2Y2 Inhibition Modifies the Anabolic Response to Exercise in Adult Mice.","authors":"Amit Chougule, Chunbin Zhang, Jordan Denbow, Nickolas Vinokurov, Devin Mendez, Elizabeth Vojtisek, Joseph Gardinier","doi":"10.1111/acel.14464","DOIUrl":"10.1111/acel.14464","url":null,"abstract":"As the aging population continues to grow, the incidence of osteoporotic fractures increases and is compounded by our lack of therapeutic strategies that increase bone formation. Although exercise and physical activity play a key role in maintaining bone mass throughout our lives, the loads and exertion required to elicit an anabolic response becomes exceedingly difficult to achieve with age. Based on previous work, the P2Y2 receptor offers a unique therapeutic target to increasing bone mass by modifying the mechanotransduction. Others have also shown P2Y2 to have a negative effect on osteoblast function. However, the extent to which inhibiting P2Y2 pharmaceutically improves bone mass or the mechanotransduction of bone remains unknown. Our central hypothesis for this study states that inhibiting P2Y2 activity can enhance the anabolic response to loading in an aging population. To test this hypothesis, the anabolic response to exercise was examined by treating adult mice, which typically display a minimal response, with the P2Y2 inhibitor AR-C118925XX (ARC). Our findings from this study demonstrate that ARC treatment of adult mice increases periosteal bone formation in response to exercise. The enhanced response to exercise was characterized by a reduction in osteocytes' induction of osteoclast activity. Endocortical bone formation also increased with treatment independently of exercise, providing gains in mechanical strength and tissue level properties. Overall, inhibiting P2Y2 activation has a beneficial effect on bone formation and the anabolic response to loading, namely by limiting osteoclast activation.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14464"},"PeriodicalIF":8.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0