Aging Cell最新文献_第5页

Hippocampal Nogo66-NgR1 signaling activation restricts postsynaptic assembly in aged mice with postoperative neurocognitive disorders. 海马 Nogo66-NgR1 信号激活限制了术后神经认知障碍老年小鼠的突触后装配。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-16 DOI: 10.1111/acel.14366

Min Jia, Gui-Zhou Li, Jiang Chen, Xiao-Hui Tang, Yan-Yu Zang, Guo-Lin Yang, Yun Stone Shi, Daqing Ma, Mu-Huo Ji, Jian-Jun Yang

{"title":"Hippocampal Nogo66-NgR1 signaling activation restricts postsynaptic assembly in aged mice with postoperative neurocognitive disorders.","authors":"Min Jia, Gui-Zhou Li, Jiang Chen, Xiao-Hui Tang, Yan-Yu Zang, Guo-Lin Yang, Yun Stone Shi, Daqing Ma, Mu-Huo Ji, Jian-Jun Yang","doi":"10.1111/acel.14366","DOIUrl":"https://doi.org/10.1111/acel.14366","url":null,"abstract":"Postoperative neurocognitive disorders (pNCD) are a common neurological complication, especially in elderly following anesthesia and surgery. Yet, the underlying mechanisms of pNCD remain elusive. This study aimed to investigate the molecular mechanisms that compromise synaptic metaplasticity in pNCD development with a focus on the involvement of Nogo-66 receptor 1 (NgR1) in the pathogenesis of pNCD in aged mice. Aged mice subjected to anesthesia and laparotomy surgery exhibited anxiety-like behavior and contextual fear memory impairment. Moreover, the procedure significantly increased NogoA and NgR1 expressions, particularly in the hippocampal CA1 and CA3 regions. This increase led to the depolymerization of F-actin, attributed to the activation of the RhoA-GTPase, resulting in a reduction of dendritic spines and changes in their morphology. Additionally, these changes hindered the efficient postsynaptic delivery of the subunit GluA1 and GluA2 of AMPA receptors (AMPARs), consequently diminishing excitatory neurotransmission in the hippocampus. Importantly, administering the competitive NgR1 antagonist peptide NEP1-40 (Nogo-A extracellular peptide residues 1-40 amino acids of Nogo-66) and Fasudil (a Rho-kinase inhibitor) effectively mitigated synaptic impairments and reversed neurocognitive deficits in aged mice following anesthesia and surgery. Our work indicates that high hippocampal Nogo66-NgR1 signaling disrupts postsynaptic AMPA receptor surface delivery due to F-actin depolymerization in the pathophysiology of pNCD.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14366"},"PeriodicalIF":8.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453915","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

Ketogenic β-hydroxybutyrate regulates β-hydroxybutyrylation of TCA cycle-associated enzymes and attenuates disease-associated pathologies in Alzheimer's mice. 生酮β-羟丁酸调节TCA循环相关酶的β-羟丁酸化，减轻阿尔茨海默氏症小鼠与疾病相关的病理变化。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-16 DOI: 10.1111/acel.14368

Wanhong Han, Bingchang Zhang, Wenpeng Zhao, Wentao Zhao, Jiawei He, Xiansheng Qiu, Liang Zhang, Xiuyan Wang, Yong Wang, Hanwen Lu, Yaya Zhang, Yuanyuan Xie, Yanyan Geng, Wujie Zhao, Qionghui Huang, Yun-Wu Zhang, Zhanxiang Wang

{"title":"Ketogenic β-hydroxybutyrate regulates β-hydroxybutyrylation of TCA cycle-associated enzymes and attenuates disease-associated pathologies in Alzheimer's mice.","authors":"Wanhong Han, Bingchang Zhang, Wenpeng Zhao, Wentao Zhao, Jiawei He, Xiansheng Qiu, Liang Zhang, Xiuyan Wang, Yong Wang, Hanwen Lu, Yaya Zhang, Yuanyuan Xie, Yanyan Geng, Wujie Zhao, Qionghui Huang, Yun-Wu Zhang, Zhanxiang Wang","doi":"10.1111/acel.14368","DOIUrl":"https://doi.org/10.1111/acel.14368","url":null,"abstract":"Lysine β-hydroxybutyrylation (Kbhb) is a post-translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label-free β-hydroxybutylation quantitative proteomics using brain samples of 8-month-old and 2-month-old APP/PS1 AD model mice and wild-type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle-associated enzymes including citrate synthase (CS) and succinate-CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium β-hydroxybutyrate (Na-β-OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that β-OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased β-OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated β-amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14368"},"PeriodicalIF":8.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453916","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

Aβ -induced excessive mitochondrial fission drives type H blood vessels injury to aggravate bone loss in APP/PS1 mice with Alzheimer's diseases. Aβ诱导的线粒体过度分裂促使H型血管损伤，加剧了阿尔茨海默病APP/PS1小鼠的骨质流失。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-16 DOI: 10.1111/acel.14374

Weidong Zhang, Fan Ding, Xing Rong, Qinghua Ren, Tomoka Hasegawa, Hongrui Liu, Minqi Li

{"title":"Aβ -induced excessive mitochondrial fission drives type H blood vessels injury to aggravate bone loss in APP/PS1 mice with Alzheimer's diseases.","authors":"Weidong Zhang, Fan Ding, Xing Rong, Qinghua Ren, Tomoka Hasegawa, Hongrui Liu, Minqi Li","doi":"10.1111/acel.14374","DOIUrl":"https://doi.org/10.1111/acel.14374","url":null,"abstract":"Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with bone homeostasis. However, few studies have concentrated on bone vascular alteration and its role in AD-related bone loss. In this study, APP/PS1 mice (4- and 8-month-old) and age-matched wild-type mice were used to assess the bone vascular alteration and its role in AD-related bone loss. Transmission electron microscopy, immunofluorescence staining and iGPS 1.0 software database were utilized to investigate the molecular mechanism. Mitochondrial division inhibitor (Mdivi-1) and GSK-3β inhibitor (LiCl) were used to rescue type H blood vessels injury and verify the molecular mechanism. Our results revealed that APP/PS1 mice exhibited more serious bone blood vessels injury and bone loss during ageing. The bone blood vessel injury, especially in type H blood vessels, was accompanied by impaired vascularized osteogenesis in APP/PS1 mice. Further exploration indicated that beta-amyloid (Aβ) promoted the apoptosis of vascular endothelial cells (ECs) and resulted in type H blood vessels injury. Mechanistically, Aβ-induced excessive mitochondrial fission was found to be essential for the apoptosis of ECs. GSK-3β was identified as a key regulatory target of Aβ-induced excessive mitochondrial fission and bone loss. The findings delineated that Aβ-induced excessive mitochondrial fission drives type H blood vessels injury, leading to aggravate bone loss in APP/PS1 mice and GSK-3β inhibitor emerges as a potential therapeutic strategy.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14374"},"PeriodicalIF":8.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453914","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

The translation initiation factor eIF2α regulates lipid homeostasis and metabolic aging. 翻译起始因子 eIF2α 调节脂质平衡和代谢衰老。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-15 DOI: 10.1111/acel.14348

Haipeng Huang, Yilie Liao, Ning Li, Xingfan Qu, Chaocan Li, Jiaqi Hou

引用次数: 0

The N6-methyladenosine landscape of ovarian development and aging highlights the regulation by RNA stability and chromatin state. 卵巢发育和衰老的 N6-甲基腺苷图谱突出了 RNA 稳定性和染色质状态的调控作用。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-15 DOI: 10.1111/acel.14376

Xiujuan Hu, Jiafeng Lu, Chenyue Ding, Jincheng Li, Qinyan Zou, Wenjuan Xia, Chunfeng Qian, Hong Li, Boxian Huang

{"title":"The N6-methyladenosine landscape of ovarian development and aging highlights the regulation by RNA stability and chromatin state.","authors":"Xiujuan Hu, Jiafeng Lu, Chenyue Ding, Jincheng Li, Qinyan Zou, Wenjuan Xia, Chunfeng Qian, Hong Li, Boxian Huang","doi":"10.1111/acel.14376","DOIUrl":"https://doi.org/10.1111/acel.14376","url":null,"abstract":"The versatile epigenetic modification known as N6-methyladenosine (m6A) has been demonstrated to be pivotal in numerous physiological and pathological contexts. Nonetheless, the precise regulatory mechanisms linking m6A to histone modifications and the involvement of transposable elements (TEs) in ovarian development and aging are still not completely understood. First, we discovered that m6A modifications are highly expressed during ovarian aging (OA), with significant contributions from decreased m6A demethylase FTO and overexpressed m6A methyltransferase METTL16. Then, using FTO knockout mouse model and KGN cell line, we also observed that FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase SUV39H1, resulting in reduced H3K9me3 expression. The downregulation of SUV39H1 and H3K9me3 primarily activated LTR7 and LTR12, subsequently activating ERV1. This resulted in a decrease in cell proliferation, while the levels of apoptosis, cellular aging markers, and autophagy markers significantly increased in OA. In summary, our study offers intriguing insights into the role of m6A in regulating DNA epigenetics, including H3K9me3 and TEs, as well as autophagy, thereby accelerating OA.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14376"},"PeriodicalIF":8.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453922","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 therapy combining Dasatinib and Quercetin restores the chondrogenic phenotype of human osteoarthritic chondrocytes by the release of pro-anabolic mediators. 结合达沙替尼和槲皮素的衰老疗法通过释放促合成代谢介质恢复了人类骨关节炎软骨细胞的软骨表型。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-14 DOI: 10.1111/acel.14361

Svenja Maurer, Valeria Kirsch, Leonie Ruths, Rolf E Brenner, Jana Riegger

{"title":"Senolytic therapy combining Dasatinib and Quercetin restores the chondrogenic phenotype of human osteoarthritic chondrocytes by the release of pro-anabolic mediators.","authors":"Svenja Maurer, Valeria Kirsch, Leonie Ruths, Rolf E Brenner, Jana Riegger","doi":"10.1111/acel.14361","DOIUrl":"https://doi.org/10.1111/acel.14361","url":null,"abstract":"Cellular senescence is associated with various age-related disorders and is assumed to play a major role in the pathogenesis of osteoarthritis (OA). Based on this, we tested a senolytic combination therapy using Dasatinib (D) and Quercetin (Q) on aged isolated human articular chondrocytes (hACs), as well as in OA-affected cartilage tissue (OARSI grade 1-2). Stimulation with D + Q selectively eliminated senescent cells in both, cartilage explants and isolated hAC. Furthermore, the therapy significantly promoted chondroanabolism, as demonstrated by increased gene expression levels of COL2A1, ACAN, and SOX9, as well as elevated collagen type II and glycosaminoglycan biosynthesis. Additionally, D + Q treatment significantly reduced the release of SASP factors (IL6, CXCL1). RNA sequencing analysis revealed an upregulation of the anabolic factors, inter alia, FGF18, IGF1, and TGFB2, as well as inhibitory effects on cytokines and the YAP-1 signaling pathway, explaining the underlying mechanism of the chondroanabolic promotion upon senolytic treatment. Accordingly, stimulation of untreated hAC with conditioned medium of D + Q-treated cells similarly induced the expression of chondrogenic markers. Detailed analyses demonstrated that chondroanabolic effects could be mainly attributed to Dasatinib, while monotherapeutical application of Quercetin or Navitoclax did not promote the chondroanabolism. Overall, D + Q therapy restored the chondrogenic phenotype in OA hAC most likely by creating a pro-chondroanabolic environment through the reduction of SASP factors and upregulation of growth factors. This senolytic approach could therefore be a promising candidate for further testing as a disease-modifying osteoarthritis drug.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14361"},"PeriodicalIF":8.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453920","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

Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells. 脂质过氧化产物会诱发人类和鼠类细胞的羰基压力、线粒体功能障碍和细胞衰老。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-11 DOI: 10.1111/acel.14367

T Blake Monroe, Ann V Hertzel, Deborah M Dickey, Thomas Hagen, Simon Vergara Santibanez, Islam A Berdaweel, Catherine Halley, Patrycja Puchalska, Ethan J Anderson, Christina D Camell, Paul D Robbins, David A Bernlohr

{"title":"Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells.","authors":"T Blake Monroe, Ann V Hertzel, Deborah M Dickey, Thomas Hagen, Simon Vergara Santibanez, Islam A Berdaweel, Catherine Halley, Patrycja Puchalska, Ethan J Anderson, Christina D Camell, Paul D Robbins, David A Bernlohr","doi":"10.1111/acel.14367","DOIUrl":"https://doi.org/10.1111/acel.14367","url":null,"abstract":"Lipid enals are electrophilic products of lipid peroxidation that induce genotoxic and proteotoxic stress by covalent modification of DNA and proteins, respectively. As lipid enals accumulate to substantial amounts in visceral adipose during obesity and aging, we hypothesized that biogenic lipid enals may represent an endogenously generated, and therefore physiologically relevant, senescence inducers. To that end, we identified that 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE) or 4-oxo-2-nonenal (4-ONE) initiate the cellular senescence program of IMR90 fibroblasts and murine adipose stem cells. In such cells, lipid enals induced accumulation of γH2AX foci, increased p53 signaling, enhanced expression of p21Cip1, and upregulated the expression and secretion of numerous cytokines, chemokines, and regulatory factors independently from NF-κB activation. Concomitantly, lipid enal treatment resulted in covalent modification of mitochondrial proteins, reduced mitochondrial spare respiratory capacity, altered nucleotide pools, and increased the phosphorylation of AMP kinase. Lipid-induced senescent cells upregulated BCL2L1 (Bcl-xL) and BCL2L2 (Bcl-w). and were resistant to apoptosis while pharmacologic inhibition of BAX/BAK macropores attenuated lipid-induced senescence. In situ, the 4-HNE scavenger L-carnosine ameliorated the development of the cellular senescence, while in visceral fat of obese C57BL/6J mice, L-carnosine reduced the abundance of 4-HNE-modified proteins and blunted the expression of senescence biomarkers CDKN1A (p21Cip1), PLAUR, BCL2L1, and BCL2L2. Taken together, the results suggest that lipid enals are endogenous regulators of cellular senescence and that biogenic lipid-induced senescence (BLIS) may represent a mechanistic link between oxidative stress and age-dependent pathologies.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14367"},"PeriodicalIF":8.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453917","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

Contextualizing aging clocks and properly describing biological age. 将老化时钟与正确描述生物年龄联系起来。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-11 DOI: 10.1111/acel.14377

Adiv A Johnson, Maxim N Shokhirev

{"title":"Contextualizing aging clocks and properly describing biological age.","authors":"Adiv A Johnson, Maxim N Shokhirev","doi":"10.1111/acel.14377","DOIUrl":"https://doi.org/10.1111/acel.14377","url":null,"abstract":"Usage of the phrase \"biological age\" has picked up considerably since the advent of aging clocks and it has become commonplace to describe an aging clock's output as biological age. In contrast to this labeling, biological age is also often depicted as a more abstract concept that helps explain how individuals are aging internally, externally, and functionally. Given that the bulk of molecular aging is tissue-specific and aging itself is a remarkably complex, multifarious process, it is unsurprising that most surveyed scientists agree that aging cannot be quantified via a single metric. We share this sentiment and argue that, just like it would not be reasonable to assume that an individual with an ideal grip strength, VO2 max, or any other aging biomarker is biologically young, we should be careful not to conflate an aging clock with whole-body biological aging. To address this, we recommend that researchers describe the output of an aging clock based on the type of input data used or the name of the clock itself. Epigenetic aging clocks produce epigenetic age, transcriptomic aging clocks produce transcriptomic age, and so forth. If a clock has a unique name, such as our recently developed epigenetic aging clock CheekAge, the name of the clock can double as the output. As a compromise solution, aging biomarkers can be described as indicators of biological age. We feel that these recommendations will help scientists and the public differentiate between aging biomarkers and the much more elusive concept of biological age.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14377"},"PeriodicalIF":8.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398785","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

CaMKIIα-TARPγ8 signaling mediates hippocampal synaptic impairment in aging. CaMKIIα-TARPγ8信号传导介导衰老过程中的海马突触损伤

IF 8 1区医学

Aging Cell Pub Date : 2024-10-08 DOI: 10.1111/acel.14349

Zhao JianHua, MingCan Li, Qilin Hu, Peter Donoghue, Sanwei Jiang, Junmei Li, Songji Li, Xinyi Ren, Ziyuan Zhang, Jingzhi Du, Yi Yu, Paul Chazot, Chengbiao Lu

{"title":"CaMKIIα-TARPγ8 signaling mediates hippocampal synaptic impairment in aging.","authors":"Zhao JianHua, MingCan Li, Qilin Hu, Peter Donoghue, Sanwei Jiang, Junmei Li, Songji Li, Xinyi Ren, Ziyuan Zhang, Jingzhi Du, Yi Yu, Paul Chazot, Chengbiao Lu","doi":"10.1111/acel.14349","DOIUrl":"https://doi.org/10.1111/acel.14349","url":null,"abstract":"Aging-related decline in memory and synaptic function are associated with the dysregulation of calcium homeostasis, attributed to the overexpression of voltage-gated calcium channels (VGCC). The membrane insertion of AMPAR governed by the AMPAR auxiliary proteins is essential for synaptic transmission and plasticity (LTP). In this study, we demonstrated the hippocampal expression of the transmembrane AMPAR regulatory proteins γ-8 (TARPγ8) was reduced in aged mice along with the reduced CaMKIIα activity and memory impairment. We further showed that TARPγ8 expression was dependent on CaMKIIα activity. Inhibition of CaMKIIα activity significantly reduced the hippocampal TARPγ8 expression and CA3-CA1 LTP in young mice to a similar level to that of the aged mice. Furthermore, the knockdown of hippocampal TARPγ8 impaired LTP and memory in young mice, which mimicked the aging-related changes. We confirmed the enhanced hippocampal VGCC (Cav-1.3) expression in aged mice and found that inhibition of VGCC activity largely increased both p-CaMKIIα and TARPγ8 expression in aged mice, whereas inhibition of NMDAR or Calpains had no effect. In addition, we found that the exogenous expression of human TARPγ8 in the hippocampus in aged mice restored LTP and memory function. Collectively, these results indicate that the synaptic and cognitive impairment in aging is associated with the downregulation of CaMKIIα-TARPγ8 signaling caused by VGCC activation. Our results suggest that TARPγ8 may be a key molecular biomarker for brain aging and that boosting CaMKIIα-TARPγ8 signaling may be critical for the restoration of synaptic plasticity of aging and aging-related diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14349"},"PeriodicalIF":8.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386559","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

Increased levels of extracellular matrix proteins associated with extracellular vesicles from brains of aged mice. 老龄小鼠大脑中与细胞外囊泡相关的细胞外基质蛋白含量增加。

IF 8 1区医学

Aging Cell Pub Date : 2024-10-08 DOI: 10.1111/acel.14359

Azariah K Kaplelach, Charles F Murchison, Kyoko Kojima, James A Mobley, Andrew E Arrant

{"title":"Increased levels of extracellular matrix proteins associated with extracellular vesicles from brains of aged mice.","authors":"Azariah K Kaplelach, Charles F Murchison, Kyoko Kojima, James A Mobley, Andrew E Arrant","doi":"10.1111/acel.14359","DOIUrl":"https://doi.org/10.1111/acel.14359","url":null,"abstract":"Extracellular vesicles (EVs) are secreted by all major cell types of the brain, providing a mode of intercellular communication and a pathway for disposal of cellular debris. EVs help maintain healthy brain function, but may also contribute to diseases affecting the brain. EVs might contribute to aging of the brain, as aging-related processes such as inflammation and cellular senescence may alter EV cargo, promoting further inflammation and senescence. However, the effects of aging on brain EVs and the function of EVs in the aging brain remain poorly understood. To address this question, we measured the levels and protein cargo of EVs isolated from the brains of 4-, 12-, and 22-month-old C57BL/6J mice. We detected no changes in EV levels, but observed age-dependent changes in EV proteins. EV fractions from aged (22 month old) brains contained higher levels of extracellular matrix proteins than EV fractions from young (4 month old) brains, with intermediate levels in 12-month-old brains. Specifically, EV fractions from aged mice contained elevated levels of hyaluronan and proteoglycan link proteins 1 and 2 and several chondroitin sulfate proteoglycans (CSPGs). Analysis of extracellular matrix in several brain regions of aged mice revealed increased immunolabeling for the CSPG aggrecan, but reduced labeling with Wisteria floribunda agglutinin, which binds to chondroitin sulfate side chains of CSPGs. These data are consistent with prior studies showing changes to the composition of extracellular matrix in aged brains, and indicate a novel association of EVs with changes in the extracellular matrix of the aging brain.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14359"},"PeriodicalIF":8.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386562","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