Aging Cell最新文献_第9页

Chromatin-transcription interface: The secret of eternal youth? 染色质-转录界面:永葆青春的秘密?

IF 7.8 1区医学

Aging Cell Pub Date : 2023-07-10 DOI: 10.1111/acel.13927

José M. Izquierdo

引用次数: 0

Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice 长期补充NAD+可防止小鼠年龄相关性听力损失的进展

IF 7.8 1区医学

Aging Cell Pub Date : 2023-07-03 DOI: 10.1111/acel.13909

Mustafa N. Okur, Burcin Duan Sahbaz, Risako Kimura, Uri Manor, Jaimin Patel, Jae-Hyeon Park, Leo Andrade, Chandrakala Puligilla, Deborah L. Croteau, Vilhelm A. Bohr

{"title":"Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice","authors":"Mustafa N. Okur, Burcin Duan Sahbaz, Risako Kimura, Uri Manor, Jaimin Patel, Jae-Hyeon Park, Leo Andrade, Chandrakala Puligilla, Deborah L. Croteau, Vilhelm A. Bohr","doi":"10.1111/acel.13909","DOIUrl":"https://doi.org/10.1111/acel.13909","url":null,"abstract":"Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6779025","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: 1

Chromosome-level Asian elephant genome assembly and comparative genomics of long-lived mammals reveal the common substitutions for cancer resistance 染色体水平的亚洲象基因组组装和长寿哺乳动物的比较基因组学揭示了癌症抗性的共同替代

IF 7.8 1区医学

Aging Cell Pub Date : 2023-07-03 DOI: 10.1111/acel.13917

Xuanjing Li, Pengcheng Wang, Qi Pan, Gaoming Liu, Weiqiang Liu, Olatunde Omotoso, Juan Du, Zihao Li, Yang Yu, Yun Huang, Pingfen Zhu, Meng Li, Xuming Zhou

{"title":"Chromosome-level Asian elephant genome assembly and comparative genomics of long-lived mammals reveal the common substitutions for cancer resistance","authors":"Xuanjing Li, Pengcheng Wang, Qi Pan, Gaoming Liu, Weiqiang Liu, Olatunde Omotoso, Juan Du, Zihao Li, Yang Yu, Yun Huang, Pingfen Zhu, Meng Li, Xuming Zhou","doi":"10.1111/acel.13917","DOIUrl":"https://doi.org/10.1111/acel.13917","url":null,"abstract":"The naked mole rat (Heterocephalus glaber), bats (e.g., genus Myotis), and elephants (family Elephantidae) are known as long-lived mammals and are assumed to be excellent cancer antagonists. However, whether there are common genetic changes underpinning cancer resistance in these long-lived species is yet to be fully established. Here, we newly generated a high-quality chromosome-level Asian elephant (Elephas maximus) genome and identified that the expanded gene families in elephants are involved in Ras-associated and base excision repair pathways. Moreover, we performed comparative genomic analyses of 12 mammals and examined genes with signatures of positive selection in elephants, naked mole rat, and greater horseshoe bat. Residues at positively selected sites of CDR2L and ALDH6A1 in these long-lived mammals enhanced the inhibition of tumor cell migration compared to those in short-lived relatives. Overall, our study provides a new genome resource and a preliminary survey of common genetic changes in long-lived mammals.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6779019","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

Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant “autophagy checkpoint” 酰基辅酶A结合蛋白(ACBP):衰老和疾病相关的“自噬检查点”

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-26 DOI: 10.1111/acel.13910

Léa Montégut, Mahmoud Abdellatif, Omar Moti?o, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos López-Otín, Guido Kroemer

{"title":"Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant “autophagy checkpoint”","authors":"Léa Montégut, Mahmoud Abdellatif, Omar Moti?o, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos López-Otín, Guido Kroemer","doi":"10.1111/acel.13910","DOIUrl":"https://doi.org/10.1111/acel.13910","url":null,"abstract":"Acyl coenzyme A binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a phylogenetically ancient protein present in some eubacteria and the entire eukaryotic radiation. In several eukaryotic phyla, ACBP/DBI transcends its intracellular function in fatty acid metabolism because it can be released into the extracellular space. This ACBP/DBI secretion usually occurs in response to nutrient scarcity through an autophagy-dependent pathway. ACBP/DBI and its peptide fragments then act on a range of distinct receptors that diverge among phyla, namely metabotropic G protein-coupled receptor in yeast (and likely in the mammalian central nervous system), a histidine receptor kinase in slime molds, and ionotropic gamma-aminobutyric acid (GABA)A receptors in mammals. Genetic or antibody-mediated inhibition of ACBP/DBI orthologs interferes with nutrient stress-induced adaptations such as sporulation or increased food intake in multiple species, as it enhances lifespan or healthspan in yeast, plant leaves, nematodes, and multiple mouse models. These lifespan and healthspan-extending effects of ACBP/DBI suppression are coupled to the induction of autophagy. Altogether, it appears that neutralization of extracellular ACBP/DBI results in “autophagy checkpoint inhibition” to unleash the anti-aging potential of autophagy. Of note, in humans, ACBP/DBI levels increase in various tissues, as well as in the plasma, in the context of aging, obesity, uncontrolled infection or cardiovascular, inflammatory, neurodegenerative, and malignant diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7025443","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: 1

Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation 吡咯喹啉醌通过MCM3-Keap1-Nrf2轴介导的应激反应和Fbn1上调缓解自然衰老相关骨质疏松症

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-26 DOI: 10.1111/acel.13912

Jie Li, Jing Zhang, Qi Xue, Boyang Liu, Ran Qin, Yiping Li, Yue Qiu, Rong Wang, David Goltzman, Dengshun Miao, Renlei Yang

{"title":"Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation","authors":"Jie Li, Jing Zhang, Qi Xue, Boyang Liu, Ran Qin, Yiping Li, Yue Qiu, Rong Wang, David Goltzman, Dengshun Miao, Renlei Yang","doi":"10.1111/acel.13912","DOIUrl":"https://doi.org/10.1111/acel.13912","url":null,"abstract":"Age-related osteoporosis is associated with increased oxidative stress and cellular senescence. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong antioxidant capacity; however, the effect and underlying mechanism of PQQ on aging-related osteoporosis remain unclear. The purpose of this study was to investigate whether dietary PQQ supplementation can prevent osteoporosis caused by natural aging, and the potential mechanism underlying PQQ antioxidant activity. Here, we found that when 6-month-old or 12-month-old wild-type mice were supplemented with PQQ for 12 months or 6 months, respectively, PQQ could prevent age-related osteoporosis in mice by inhibiting osteoclastic bone resorption and stimulating osteoblastic bone formation. Mechanistically, pharmmapper screening and molecular docking studies revealed that PQQ appears to bind to MCM3 and reduces its ubiquitination-mediated degradation; stabilized MCM3 then competes with Nrf2 for binding to Keap1, thus activating Nrf2-antioxidant response element (ARE) signaling. PQQ-induced Nrf2 activation inhibited bone resorption through increasing stress response capacity and transcriptionally upregulating fibrillin-1 (Fbn1), thus reducing Rankl production in osteoblast-lineage cells and decreasing osteoclast activation; as well, bone formation was stimulated by inhibiting osteoblastic DNA damage and osteocyte senescence. Furthermore, Nrf2 knockout significantly blunted the inhibitory effects of PQQ on oxidative stress, on increased osteoclast activity and on the development of aging-related osteoporosis. This study reveals the underlying mechanism of PQQ's strong antioxidant capacity and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging-induced osteoporosis.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7025445","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

Deficiency for scavenger receptors Stabilin-1 and Stabilin-2 leads to age-dependent renal and hepatic depositions of fasciclin domain proteins TGFBI and Periostin in mice 清道夫受体稳定素-1和稳定素-2的缺乏导致小鼠肌束蛋白结构域TGFBI和骨膜蛋白在肾脏和肝脏的年龄依赖性沉积

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-25 DOI: 10.1111/acel.13914

Thomas Leibing, Anna Riedel, Yannick Xi, Monica Adrian, Jessica Krzistetzko, Christof Kirkamm, Christof Dormann, Kai Schledzewski, Sergij Goerdt, Cyrill Géraud

{"title":"Deficiency for scavenger receptors Stabilin-1 and Stabilin-2 leads to age-dependent renal and hepatic depositions of fasciclin domain proteins TGFBI and Periostin in mice","authors":"Thomas Leibing, Anna Riedel, Yannick Xi, Monica Adrian, Jessica Krzistetzko, Christof Kirkamm, Christof Dormann, Kai Schledzewski, Sergij Goerdt, Cyrill Géraud","doi":"10.1111/acel.13914","DOIUrl":"https://doi.org/10.1111/acel.13914","url":null,"abstract":"Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are two major scavenger receptors of liver sinusoidal endothelial cells that mediate removal of diverse molecules from the plasma. Double-knockout mice (Stab-DKO) develop impaired kidney function and a decreased lifespan, while single Stabilin deficiency or therapeutic inhibition ameliorates atherosclerosis and Stab1-inhibition is subject of clinical trials in immuno-oncology. Although POSTN and TFGBI have recently been described as novel Stabilin ligands, the dynamics and functional implications of these ligands have not been comprehensively studied. Immunofluorescence, Western Blotting and Simple Western™ as well as in situ hybridization (RNAScope™) and qRT-PCR were used to analyze transcription levels and tissue distribution of POSTN and TGFBI in Stab-KO mice. Stab-POSTN-Triple deficient mice were generated to assess kidney and liver fibrosis and function in young and aged mice. TGFBI and POSTN protein accumulated in liver tissue in Stab-DKO mice and age-dependent in glomeruli of Stabilin-deficient mice despite unchanged transcriptional levels. Stab-POSTN-Triple KO mice showed glomerulofibrosis and a reduced lifespan comparable to Stab-DKO mice. However, alterations of the glomerular diameter and vascular density were partially normalized in Stab-POSTN-Triple KO. TGFBI and POSTN are Stabilin-ligands that are deposited in an age-dependent manner in the kidneys and liver due to insufficient scavenging in the liver. Functionally, POSTN might partially contribute to the observed renal phenotype in Stab-DKO mice. This study provides details on downstream effects how Stabilin dysfunction affects organ function on a molecular and functional level.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7018208","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: 3

Releasing YAP dysfunction-caused replicative toxicity rejuvenates mesenchymal stem cells 释放YAP功能障碍引起的复制毒性可使间充质干细胞恢复活力

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-20 DOI: 10.1111/acel.13913

Fanyuan Yu, Lin Yao, Feifei Li, Chenglin Wang, Ling Ye

{"title":"Releasing YAP dysfunction-caused replicative toxicity rejuvenates mesenchymal stem cells","authors":"Fanyuan Yu, Lin Yao, Feifei Li, Chenglin Wang, Ling Ye","doi":"10.1111/acel.13913","DOIUrl":"https://doi.org/10.1111/acel.13913","url":null,"abstract":"Hippo‐independent YAP dysfunction has been demonstrated to cause chronological aging of stromal cells by impairing the integrity of nuclear envelope (NE). In parallel with this report, we uncover that YAP activity also controls another type of cellular senescence, the replicative senescence in in vitro expansion of mesenchymal stromal cells (MSCs), but this event is Hippo phosphorylation‐dependent, and there exist another NE integrity‐independent downstream mechanisms of YAP. Specifically, Hippo phosphorylation causes reduced nuclear/active YAP and then decreases the level of YAP protein in the proceeding of replicative senescence. YAP/TEAD governs RRM2 expression to release replicative toxicity (RT) via licensing G1/S transition. Besides, YAP controls the core transcriptomics of RT to delay the onset of genome instability and enhances DNA damage response/repair. Hippo‐off mutations of YAP (YAPS127A/S381A) satisfactorily release RT via maintaining cell cycle and reducing genome instability, finally rejuvenating MSCs and restoring their regenerative capabilities without risks of tumorigenesis.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6967674","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

The role of aging and brain-derived neurotrophic factor signaling in expression of base excision repair genes in the human brain 衰老和脑源性神经营养因子信号在人脑碱基切除修复基因表达中的作用

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-19 DOI: 10.1111/acel.13905

Sofie Lautrup, Camilla Myrup?Holst, Anne Yde, Stine Asmussen, Vibeke Thinggaard, Knud Larsen, Lisbeth Schmidt Laursen, Mette Richner, Christian B. V?gter, G. Aleph Prieto, Nicole Berchtold, Carl W. Cotman, Tinna Stevnsner

{"title":"The role of aging and brain-derived neurotrophic factor signaling in expression of base excision repair genes in the human brain","authors":"Sofie Lautrup, Camilla Myrup?Holst, Anne Yde, Stine Asmussen, Vibeke Thinggaard, Knud Larsen, Lisbeth Schmidt Laursen, Mette Richner, Christian B. V?gter, G. Aleph Prieto, Nicole Berchtold, Carl W. Cotman, Tinna Stevnsner","doi":"10.1111/acel.13905","DOIUrl":"https://doi.org/10.1111/acel.13905","url":null,"abstract":"DNA damage is a central contributor to the aging process. In the brain, a major threat to the DNA is the considerable amount of reactive oxygen species produced, which can inflict oxidative DNA damage. This type of damage is removed by the base excision repair (BER) pathway, an essential DNA repair mechanism, which contributes to genome stability in the brain. Despite the crucial role of the BER pathway, insights into how this pathway is affected by aging in the human brain and the underlying regulatory mechanisms are very limited. By microarray analysis of four cortical brain regions from humans aged 20–99 years (n = 57), we show that the expression of core BER genes is largely downregulated during aging across brain regions. Moreover, we find that expression of many BER genes correlates positively with the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in the human brain. In line with this, we identify binding sites for the BDNF-activated transcription factor, cyclic-AMP response element-binding protein (CREB), in the promoter of most BER genes and confirm the ability of BDNF to regulate several BER genes by BDNF treatment of mouse primary hippocampal neurons. Together, these findings uncover the transcriptional landscape of BER genes during aging of the brain and suggest BDNF as an important regulator of BER in the human brain.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6957702","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

Deletion of enzymes for de novo NAD+ biosynthesis accelerated ovarian aging 新生NAD+生物合成酶的缺失加速了卵巢衰老

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-18 DOI: 10.1111/acel.13904

Qingling Yang, Hui Li, Huan Wang, Wenhui Chen, Xinxin Zeng, Xiaoyan Luo, Jianmin Xu, Yingpu Sun

{"title":"Deletion of enzymes for de novo NAD+ biosynthesis accelerated ovarian aging","authors":"Qingling Yang, Hui Li, Huan Wang, Wenhui Chen, Xinxin Zeng, Xiaoyan Luo, Jianmin Xu, Yingpu Sun","doi":"10.1111/acel.13904","DOIUrl":"https://doi.org/10.1111/acel.13904","url":null,"abstract":"Recent advances highlight the pivotal role of nicotinamide adenine dinucleotide (NAD+) in ovarian aging. However, the roles of de novo NAD+ biosynthesis on ovarian aging are still unknown. Here, we found that genetic ablation of Ido1 (indoleamine-2,3-dioxygenase 1) or Qprt (Quinolinate phosphoribosyl transferase), two critical genes in de novo NAD+ biosynthesis, resulted in decreased ovarian NAD+ levels in middle-aged mice, leading to subfertility, irregular estrous cycles, reduced ovarian reserve, and accelerated aging. Moreover, we observed impaired oocyte quality, characterized by increased reactive oxygen species and spindle anomalies, which ultimately led to reduced fertilization ability and impaired early embryonic development. A transcriptomic analysis of ovaries in both mutant and wild-type mice revealed alterations in gene expression related to mitochondrial metabolism. Our findings were further supported by the observation of impaired mitochondrial distribution and decreased mitochondrial membrane potential in the oocytes of knockout mice. Supplementation with nicotinamide riboside (NR), an NAD+ booster, in mutant mice increased ovarian reserve and improved oocyte quality. Our study highlights the importance of the NAD+ de novo pathway in middle-aged female fertility.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6951193","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

A rationally designed fluorescence probe achieves highly specific and long-term detection of senescence in vitro and in vivo 合理设计的荧光探针，在体外和体内实现了对衰老的高度特异性和长效检测

IF 7.8 1区医学

Aging Cell Pub Date : 2023-06-13 DOI: 10.1111/acel.13896

Li Hu, Chanjuan Dong, Zhe Wang, Shengyuan He, Yiwen Yang, Meiting Zi, Huiqin Li, Yanghuan Zhang, Chuanjie Chen, Runzi Zheng, Shuting Jia, Jing Liu, Xuan Zhang, Yonghan He

{"title":"A rationally designed fluorescence probe achieves highly specific and long-term detection of senescence in vitro and in vivo","authors":"Li Hu, Chanjuan Dong, Zhe Wang, Shengyuan He, Yiwen Yang, Meiting Zi, Huiqin Li, Yanghuan Zhang, Chuanjie Chen, Runzi Zheng, Shuting Jia, Jing Liu, Xuan Zhang, Yonghan He","doi":"10.1111/acel.13896","DOIUrl":"https://doi.org/10.1111/acel.13896","url":null,"abstract":"Senescent cells (SnCs) are implicated in aging and various age-related pathologies. Targeting SnCs can treat age-related diseases and extend health span. However, precisely tracking and visualizing of SnCs is still challenging, especially in in vivo environments. Here, we developed a near-infrared (NIR) fluorescent probe (XZ1208) that targets β-galactosidase (β-Gal), a well-accepted biomarker for cellular senescence. XZ1208 can be cleaved rapidly by β-Gal and produces a strong fluorescence signal in SnCs. We demonstrated the high specificity and sensitivity of XZ1208 in labeling SnCs in naturally aged, total body irradiated (TBI), and progeroid mouse models. XZ1208 achieved a long-term duration of over 6 days in labeling senescence without causing significant toxicities and accurately detected the senolytic effects of ABT263 on eliminating SnCs. Furthermore, XZ1208 was applied to monitor SnCs accumulated in fibrotic diseases and skin wound healing models. Overall, we developed a tissue-infiltrating NIR probe and demonstrated its excellent performance in labeling SnCs in aging and senescence-associated disease models, indicating great potential for application in aging studies and diagnosis of senescence-associated diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 8","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5839972","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: 1