Aging Cell最新文献_第5页

V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging. 酵母菌溶酶体样液泡中的v - atp酶拆卸是复制衰老中溶酶体功能障碍的表型驱动因素。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-16 DOI: 10.1111/acel.14487

Fiza Hashmi, Patricia M Kane

{"title":"V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.","authors":"Fiza Hashmi, Patricia M Kane","doi":"10.1111/acel.14487","DOIUrl":"https://doi.org/10.1111/acel.14487","url":null,"abstract":"Declines in lysosomal acidification and function with aging are observed in organisms ranging from yeast to humans. V-ATPases play a central role in organelle acidification, and V-ATPase activity is regulated by reversible disassembly in many different settings. Using the yeast Saccharomyces cerevisiae as a replicative aging model, we demonstrate that V-ATPases disassemble into their V1 and V0 subcomplexes in aging cells, with release of V1 subunit C (Vma5) from the lysosome-like vacuole into the cytosol. Disassembly is observed after > 5 cell divisions and results in overall vacuole alkalinization. Caloric restriction, an established mechanism for reversing many age-related outcomes, prevents V-ATPase disassembly in older cells and preserves vacuolar pH homeostasis. Reversible disassembly is controlled in part by the activity of two opposing and conserved factors: the Regulator of Acidification of Vacuoles and Endosomes (RAVE) complex and Oxr1. The RAVE complex promotes V-ATPase assembly and a rav1∆ mutant shortens replicative lifespan; Oxr1 promotes disassembly and an oxr1∆ mutation extends the lifespan. Importantly, the level of Rav2, a subunit of the RAVE complex, declines in aged cells, and Rav2 overexpression delays V-ATPase disassembly with age. These data indicate that reduced V-ATPase assembly contributes to the loss of lysosomal acidification with age, which affects replicative lifespan.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14487"},"PeriodicalIF":8.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996699","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

Low-Intensity Pulsed Ultrasound Treatment Selectively Stimulates Senescent Cells to Promote SASP Factors for Immune Cell Recruitment. 低强度脉冲超声治疗选择性刺激衰老细胞促进免疫细胞募集的SASP因子。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-16 DOI: 10.1111/acel.14486

HyeRan Gwak, Seoyoung Hong, Su Hyun Lee, In Woo Kim, Yonghan Kim, Hyungmin Kim, Ki Joo Pahk, So Yeon Kim

{"title":"Low-Intensity Pulsed Ultrasound Treatment Selectively Stimulates Senescent Cells to Promote SASP Factors for Immune Cell Recruitment.","authors":"HyeRan Gwak, Seoyoung Hong, Su Hyun Lee, In Woo Kim, Yonghan Kim, Hyungmin Kim, Ki Joo Pahk, So Yeon Kim","doi":"10.1111/acel.14486","DOIUrl":"https://doi.org/10.1111/acel.14486","url":null,"abstract":"As emerging therapeutic strategies for aging and age-associated diseases, various biochemical approaches have been developed to selectively remove senescent cells, but how physical stimulus influences senescent cells and its possible application in senolytic therapy has not been reported yet. Here we developed a physical method to selectively stimulate senescent cells via low-intensity pulsed ultrasound (LIPUS) treatment. LIPUS stimulation did not affect the cell cycle, but selectively enhanced secretion of specific cytokines in senescent cells, known as the senescence-associated secretory phenotype (SASP), resulting in enhanced migration of monocytes/macrophages and upregulation of phagocytosis of senescent cells by M1 macrophage. We found that LIPUS stimulation selectively perturbed the cellular membrane structure in senescent cells, which led to activation of the intracellular reactive oxygen species-dependent p38-NF-κB signaling pathway. Using a UV-induced skin aging mouse model, we confirmed enhanced macrophage infiltration followed by reduced senescent cells after LIPUS treatment. Due to the advantages of ultrasound treatment, such as non-invasiveness, deep penetration capability, and easy application in clinical settings, we expect that our method can be applied to treat various senescence-associated diseases or combined with other established biochemical therapies to enhance efficacy.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14486"},"PeriodicalIF":8.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996693","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

Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV. 血浆蛋白质组学特征作为HIV感染者年龄增长的预测因子。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-15 DOI: 10.1111/acel.14468

Adriana Navas, Vasiliki Matzaraki, Louise E van Eekeren, Marc J T Blaauw, Albert L Groenendijk, Wilhelm A J W Vos, Maartje Jacobs-Cleophas, Jéssica C Dos Santos, André J A M van der Ven, Leo A B Joosten, Mihai G Netea

{"title":"Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV.","authors":"Adriana Navas, Vasiliki Matzaraki, Louise E van Eekeren, Marc J T Blaauw, Albert L Groenendijk, Wilhelm A J W Vos, Maartje Jacobs-Cleophas, Jéssica C Dos Santos, André J A M van der Ven, Leo A B Joosten, Mihai G Netea","doi":"10.1111/acel.14468","DOIUrl":"https://doi.org/10.1111/acel.14468","url":null,"abstract":"Due to the increased burden of non-AIDS-related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging and the risk of developing age-related comorbidities is a priority. Evidence suggests that the plasma proteome is an accurate source for measuring biological age and predicting age-related clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit a premature aging phenotype, we profiled the plasma proteome of two independent cohorts of virally suppressed PLHIV (200HIV and 2000HIV) and one cohort of people without HIV (200FG) using O-link technology. Next, we built a biological age-prediction model and correlated age advancement (the deviation of the predicted age from the chronological age) with HIV-related factors, comorbidities, and cytokines secreted by immune cells. We identified a common signature of 77 proteins associated with chronological age across all cohorts, most of which were involved in inflammatory and senescence-related processes. PLHIV showed increased age advancement compared to people without HIV. In addition, age advancement in the 2000HIV cohort was positively associated with prior hepatitis C and cytomegalovirus (CMV) infections, non-AIDS-related comorbidities, ART duration, cumulative exposure to the protease inhibitor Ritonavir, as well as higher production of monocyte-derived proinflammatory cytokines and chemokines and lower secretion of T-cell derived cytokines. Our proteome-based predictive model is a promising approach for calculating the age advancement in PLHIV. This will potentially allow for further characterization of the pathophysiological mechanisms linked to accelerated aging and enable monitoring the effectiveness of novel therapies aimed at reducing age-related diseases in PLHIV.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14468"},"PeriodicalIF":8.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982072","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

Salidroside Improves Oocyte Competence of Reproductively Old Mice by Enhancing Mitophagy. 红身草苷通过促进线粒体自噬提高生殖老龄小鼠卵母细胞能力。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-09 DOI: 10.1111/acel.14475

Jingkai Gu, Renwu Hua, Huayan Wu, Chenxi Guo, Zhuo Hai, Yuan Xiao, William S B Yeung, Kui Liu, Elnur Babayev, Tianren Wang

引用次数: 0

Cross-tissue comparison of epigenetic aging clocks in humans. 人类表观遗传衰老时钟的跨组织比较。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-09 DOI: 10.1111/acel.14451

Abner T Apsley, Qiaofeng Ye, Avshalom Caspi, Christopher Chiaro, Laura Etzel, Waylon J Hastings, Christine M Heim, John Kozlosky, Jennie G Noll, Hannah M C Schreier, Chad E Shenk, Karen Sugden, Idan Shalev

{"title":"Cross-tissue comparison of epigenetic aging clocks in humans.","authors":"Abner T Apsley, Qiaofeng Ye, Avshalom Caspi, Christopher Chiaro, Laura Etzel, Waylon J Hastings, Christine M Heim, John Kozlosky, Jennie G Noll, Hannah M C Schreier, Chad E Shenk, Karen Sugden, Idan Shalev","doi":"10.1111/acel.14451","DOIUrl":"10.1111/acel.14451","url":null,"abstract":"Epigenetic clocks are a common group of tools used to measure biological aging-the progressive deterioration of cells, tissues, and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues, but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. We tested 284 distinct tissue samples from 83 individuals aged 9-70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Notably, the Skin and Blood clock exhibited the greatest concordance across all tissue types, indicating its unique ability to estimate chronological age in oral- and blood-based tissues. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14451"},"PeriodicalIF":8.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941478","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

Cellular Senescence Contributes to the Dysfunction of Tight Junctions in Submandibular Glands of Aging Mice. 细胞衰老导致衰老小鼠颌下腺紧密连接功能障碍。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-09 DOI: 10.1111/acel.14470

Zhuo Chen, Qian-Ying Mao, Jie-Yuan Zhang, Yu-Xiao Wu, Xiao-Feng Shan, Yan Geng, Jia-Yi Fan, Zhi-Gang Cai, Ruo-Lan Xiang

{"title":"Cellular Senescence Contributes to the Dysfunction of Tight Junctions in Submandibular Glands of Aging Mice.","authors":"Zhuo Chen, Qian-Ying Mao, Jie-Yuan Zhang, Yu-Xiao Wu, Xiao-Feng Shan, Yan Geng, Jia-Yi Fan, Zhi-Gang Cai, Ruo-Lan Xiang","doi":"10.1111/acel.14470","DOIUrl":"https://doi.org/10.1111/acel.14470","url":null,"abstract":"The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs) were observed in naturally aging and D-gal mice, whereas sublingual glands (SLGs) had no notable alterations. We observed the accumulation of senescent cells in the SMGs, along with a decrease in claudin-3 (Cldn-3) expression and alterations in the distribution of Cldn1 and Cldn3. Additionally, after D-gal-induced senescence of SMG-C6 cells, there was a decrease in paracellular pathway permeability, reduced expression of Cldn3 and occludin, and changes in the distribution of Cldn1, 3, 4, and 7. Furthermore, injecting DPSC-exos into the SMGs of D-gal mice improved stimulated salivary flow rate, reduced acinar atrophy, and decreased SA-β-gal activity. Our study identified that increased senescence of SMGs in aging mice can cause a decrease in salivary secretion by disrupting the expression and distribution of tight junction molecules, and injection of DPSC-exos ameliorates SMG secretory dysfunction. These findings may provide new clues to novel therapeutic targets for aging-related dysfunction of SMGs.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14470"},"PeriodicalIF":8.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941517","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

Weakened Airway Epithelial Junctions and Enhanced Neutrophil Elastase Release Contribute to Age-Dependent Bacteremia Risk Following Pneumococcal Pneumonia. 气道上皮连接减弱和中性粒细胞弹性蛋白酶释放增强有助于肺炎球菌肺炎后年龄依赖性菌血症风险。

IF 8 1区医学

Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14474

Shuying Xu, Tianmou Zhu, Hongmei Mou, Shumin Tan, John M Leong

{"title":"Weakened Airway Epithelial Junctions and Enhanced Neutrophil Elastase Release Contribute to Age-Dependent Bacteremia Risk Following Pneumococcal Pneumonia.","authors":"Shuying Xu, Tianmou Zhu, Hongmei Mou, Shumin Tan, John M Leong","doi":"10.1111/acel.14474","DOIUrl":"10.1111/acel.14474","url":null,"abstract":"Streptococcus pneumoniae (Sp; pneumococcus), the most common agent of community-acquired pneumonia, can spread systemically, particularly in the elderly, highlighting the need for adjunctive therapies. The airway epithelial barrier defends against bacteremia and is dependent upon apical junctional complex (AJC) proteins such as E-cadherin. After mouse lung challenge, pneumolysin (PLY), a key Sp virulence factor, stimulates epithelial secretion of an inflammatory eicosanoid, triggering the infiltration of polymorphonuclear leukocytes (PMNs) that secrete high levels of neutrophil elastase (NE), thus promoting epithelial damage and systemic infection. Here, pulmonary E-cadherin staining of intratracheally (i.t.) inoculated mice revealed PLY-mediated disruption of AJC independently of PMNs. Apical infection of air-liquid interface (ALI) respiratory epithelial monolayers similarly showed that PLY disrupts AJCs. This epithelial damage promoted PMN transmigration and bacterial apical-to-basolateral translocation, and pharmacologically fortifying epithelial barrier function diminished both barrier breach in vitro and bacteremia in vivo. E-cadherin staining after Sp i.t. inoculation of > 20-month-old mice, or apical infection of ALI monolayers derived from these mice, revealed an age-associated vulnerability to PLY-mediated AJC disruption, which in turn enhanced PMN migration and bacteremia. In addition, we found that PMNs from aged mice secrete increased levels of tissue-damaging NE. Simultaneous pharmacological inhibition of tissue-destructive NE and fortification of pulmonary epithelial barrier function was required to reduce the level of Sp bacteremia in aged mice to that of young mice. This work underscores the importance of fully characterizing the multifactorial sources of age-associated susceptibility in devising adjunctive therapies to mitigate invasive pneumococcal disease in the elderly.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14474"},"PeriodicalIF":8.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941572","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

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 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":"https://doi.org/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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14476"},"PeriodicalIF":8.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14448"},"PeriodicalIF":8.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 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":"https://doi.org/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":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14425"},"PeriodicalIF":8.0,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0