Aging Cell最新文献_第7页

Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study 加速生物老化、健康行为和遗传易感性与脑卒中及其亚型的发病率：一项前瞻性队列研究

IF 7.8 1区医学

Aging Cell Pub Date : 2024-12-04 DOI: 10.1111/acel.14427

Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu

{"title":"Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study","authors":"Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu","doi":"10.1111/acel.14427","DOIUrl":"10.1111/acel.14427","url":null,"abstract":"Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA acceleration calculated by regressing BA on chronological age. The polygenic risk score (PRS) was derived from 87 genetic loci. The behaviors score was based on diet, physical activity, tobacco/nicotine, sleep, and BMI. During a median follow-up of 13.6 years, 5460 strokes, 4337 ischemic stroke (IS), 951 intracerebral hemorrhage (ICH), and 553 subarachnoid hemorrhage (SAH) cases were documented. Adjusting for confounding factors, each standard deviation increase in BA acceleration was associated with higher stroke risk: for KDM-BA acceleration, stroke (HR = 1.28, 95% CI = 1.25–1.32), IS (1.32, 1.28–1.36), ICH (1.15, 1.08–1.23), and SAH (1.16, 1.07–1.27); for PhenoAge acceleration, stroke (1.22, 1.19–1.25), IS (1.26, 1.22–1.29), ICH (1.08, 1.02–1.16), and SAH (1.08, 1.00–1.18). Compared to participants with the lowest PRS and BA acceleration, those with the highest PRS and BA acceleration had the highest stroke risk (KDM-BA acceleration: 2.19, 1.85–2.59; PhenoAge acceleration: 2.03, 1.69–2.42). Additionally, there was an additive interaction between KDM-BA acceleration and PRS. The mediation proportion of BA acceleration in associations of behaviors score with incident stroke and its subtypes ranged from 15.84% to 33.08%. BA acceleration may raise stroke risk, especially in those with high genetic risk. Maintaining healthy behaviors may help mitigate this risk.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778681","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

Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity 骨骼肌线粒体断裂预示着与年龄相关的身体能力下降。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-12-04 DOI: 10.1111/acel.14386

Richie P. Goulding, Braeden T. Charlton, Ellen A. Breedveld, Matthijs van der Laan, Anne R. Strating, Wendy Noort, Aryna Kolodyazhna, Brent Appelman, Michèle van Vugt, Anita E. Grootemaat, Nicole N. van der Wel, Jos J. de Koning, Frank W. Bloemers, Rob C. I. Wüst

{"title":"Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity","authors":"Richie P. Goulding, Braeden T. Charlton, Ellen A. Breedveld, Matthijs van der Laan, Anne R. Strating, Wendy Noort, Aryna Kolodyazhna, Brent Appelman, Michèle van Vugt, Anita E. Grootemaat, Nicole N. van der Wel, Jos J. de Koning, Frank W. Bloemers, Rob C. I. Wüst","doi":"10.1111/acel.14386","DOIUrl":"10.1111/acel.14386","url":null,"abstract":"Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals. Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle-aged: 99 ± 27 pmol O2.s−1.mg−1, p = 0.95) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle-aged: 5.68 ± 1.48%, p = 0.25), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle-aged: 1.55 ± 0.15 A.U., p < 0.0001), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle-aged: 13.55 ± 4.10%, p = 0.002) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle-aged: 13.92 ± 4.95%, p = 0.005). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density. Collectively, our work highlights the critical role of skeletal muscle mitochondria in age-associated declines in physical function.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765053","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

Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements 老年人生活方式干预与代谢和生理健康改善相关的组织特异性甲基组反应

IF 7.8 1区医学

Aging Cell Pub Date : 2024-12-01 DOI: 10.1111/acel.14431

Lucy Sinke, Marian Beekman, Yotam Raz, Thies Gehrmann, Ioannis Moustakas, Alexis Boulinguiez, Nico Lakenberg, Eka Suchiman, Fatih A. Bogaards, Daniele Bizzarri, Erik B. van den Akker, Melanie Waldenberger, Gillian Butler-Browne, Capucine Trollet, C. P. G. M. de Groot, Bastiaan T. Heijmans, P. Eline Slagboom

{"title":"Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements","authors":"Lucy Sinke, Marian Beekman, Yotam Raz, Thies Gehrmann, Ioannis Moustakas, Alexis Boulinguiez, Nico Lakenberg, Eka Suchiman, Fatih A. Bogaards, Daniele Bizzarri, Erik B. van den Akker, Melanie Waldenberger, Gillian Butler-Browne, Capucine Trollet, C. P. G. M. de Groot, Bastiaan T. Heijmans, P. Eline Slagboom","doi":"10.1111/acel.14431","DOIUrl":"10.1111/acel.14431","url":null,"abstract":"Across the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue-specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes. The Growing Old Together (GOTO) study is a 13-week lifestyle intervention in older adults, which imparted health benefits to participants. Here, we characterize the DNA methylation response to this intervention at over 750 thousand CpGs in muscle, adipose, and blood. Differentially methylated sites are enriched for active chromatin states, located close to relevant transcription factor binding sites, and associated with changing expression of insulin sensitivity genes and health parameters. In addition, measures of biological age are consistently reduced, with decreases in grimAge associated with observed health improvements. Taken together, our results identify responsive molecular markers and demonstrate their potential to measure progression and finetune treatment of age-related risks and diseases.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765094","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 ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model 帕金森病小鼠模型中脑线粒体相关内质网膜超微结构和蛋白质组学分析

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-29 DOI: 10.1111/acel.14436

Jin Liu, Yi Liu, Chao Gao, Hong Pan, Pei Huang, Yuyan Tan, Shengdi Chen

{"title":"The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model","authors":"Jin Liu, Yi Liu, Chao Gao, Hong Pan, Pei Huang, Yuyan Tan, Shengdi Chen","doi":"10.1111/acel.14436","DOIUrl":"10.1111/acel.14436","url":null,"abstract":"Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. In MPTP-treated mice, transmission electron microscopy was applied for MAM ultrastructural visualization. Nano ultra-high performance liquid chromatography-tandem mass spectrum and bioinformatic analysis were adopted to obtain underlying molecular data of MAM fractions. The loosened, shortened and reduced MAM tethering was found in substantia nigral neurons from MPTP-treated mice. In midbrain MAM proteomics, 158 differentially expressed proteins (DEPs) were identified between two groups. Specific DEPs were validated by western blot and exhibited significantly statistical changes, aligning with proteomic results. Bioinformatic analysis indicated that membrane, cytoplasm and cell projection were three major localizations for DEPs. Biological processes including metabolism, lipid transport, and immunological and apoptotic signaling pathways were greatly affected. For consensus MAM proteins, the enriched pathway analysis revealed the potential relationship between neurodegenerative diseases and MAM. Several biological processes such as peroxisome function and clathrin-mediated endocytosis, were clustered, which provided additional insights into the fundamental molecular pathways associated with MAM. In our study, we demonstrated disrupted ER-mitochondria contacts in an MPTP-induced PD mouse model. The underlying signatures of MAM were revealed by proteomics and bioinformatic analysis, providing valuable insights into its potential role in PD pathogenesis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754368","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

Restoration of hair follicle inductive properties by depletion of senescent cells 通过消耗衰老细胞恢复毛囊诱导特性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-29 DOI: 10.1111/acel.14353

Alberto Pappalardo, Jin Yong Kim, Hasan Erbil Abaci, Angela M. Christiano

{"title":"Restoration of hair follicle inductive properties by depletion of senescent cells","authors":"Alberto Pappalardo, Jin Yong Kim, Hasan Erbil Abaci, Angela M. Christiano","doi":"10.1111/acel.14353","DOIUrl":"10.1111/acel.14353","url":null,"abstract":"Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP-mediated repressive interactions in human DP culture, resulting in an increased Wnt-active cell population. In hair reconstitution assays, senolytic-depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic-depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell-based therapies.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754367","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

Piezo1 exacerbates inflammation-induced cartilaginous endplate degeneration by activating mitochondrial fission via the Ca2+/CaMKII/Drp1 axis Piezo1通过Ca2+/CaMKII/Drp1轴激活线粒体裂变，从而加剧炎症诱导的软骨终板变性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-28 DOI: 10.1111/acel.14440

Zhidi Lin, Guangyu Xu, Xiao Lu, Hongli Wang, Feizhou Lu, Xinlei Xia, Jian Song, Jianyuan Jiang, Xiaosheng Ma, Fei Zou

{"title":"Piezo1 exacerbates inflammation-induced cartilaginous endplate degeneration by activating mitochondrial fission via the Ca2+/CaMKII/Drp1 axis","authors":"Zhidi Lin, Guangyu Xu, Xiao Lu, Hongli Wang, Feizhou Lu, Xinlei Xia, Jian Song, Jianyuan Jiang, Xiaosheng Ma, Fei Zou","doi":"10.1111/acel.14440","DOIUrl":"10.1111/acel.14440","url":null,"abstract":"Mitochondrial homeostasis plays a crucial role in degenerative joint diseases, including cartilaginous endplate (CEP) degeneration. To date, research into mitochondrial dynamics in IVDD is at an early stage. Since Piezo1 is a novel Ca2+-permeable channel, we asked whether Piezo1 could modulate mitochondrial fission through Ca2+ signalling during CEP degeneration. In vitro and in vivo models of inflammation-induced CEP degeneration were established with lipopolysaccharide (LPS). We found increased expression of Piezo1 in degenerated CEP tissues and LPS-treated CEP cells. The Piezo1 activator Yoda1 exacerbated CEP cell senescence and apoptosis by triggering Ca2+ influx. Yoda1 also induced mitochondrial fragmentation and dysfunction. In contrast, the Piezo1 inhibitor GsMTx4 exerted cytoprotective effects in LPS-treated CEP cells. Additionally, the CaMKII inhibitor KN-93 reversed Yoda1-induced mitochondrial fission and restored mitochondrial function. Mechanistically, the phosphorylation and mitochondrial translocation of Drp1 were regulated by the Ca2+/CaMKII signalling. The Drp1 inhibitor Mdivi-1 suppressed mitochondrial fission, then reduced mitochondrial dysfunction and CEP cell death. Moreover, knockdown of Piezo1 by siRNA hindered CaMKII and Drp1 activation, facilitating the redistribution of mitochondrial Drp1 to the cytosol in LPS-treated CEP cells. Piezo1 silencing improved mitochondrial morphology and function, thereby rescuing CEP cell senescence and apoptosis under inflammatory conditions. Finally, subendplate injection of GsMTx4 or AAV-shPiezo1 alleviated CEP degeneration in a rat model. Thus, Piezo1 may exacerbate inflammation-induced CEP degeneration by triggering mitochondrial fission and dysfunction via the Ca2+/CaMKII/Drp1 axis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749392","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

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain 表观遗传学年龄加速预测了人脑中特定主体白质的退化。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-28 DOI: 10.1111/acel.14426

Benjamin T. Newman, Joshua S. Danoff, Morgan E. Lynch, Stephanie N. Giamberardino, Simon G. Gregory, Jessica J. Connelly, T. Jason Druzgal, James P. Morris

{"title":"Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain","authors":"Benjamin T. Newman, Joshua S. Danoff, Morgan E. Lynch, Stephanie N. Giamberardino, Simon G. Gregory, Jessica J. Connelly, T. Jason Druzgal, James P. Morris","doi":"10.1111/acel.14426","DOIUrl":"10.1111/acel.14426","url":null,"abstract":"Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions “lesioned” by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to demonstrate WMH lesionometry as a subject-specific precision imaging technique to study degeneration in aging and the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737960","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

Overlooked histories in ageing research: Pioneering women at the foundation of our field 老龄化研究中被忽视的历史：我们领域奠基人中的先驱女性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-28 DOI: 10.1111/acel.14432

Marina Ezcurra, Colin Selman, Jennifer Tullet, Nathan Woodling

{"title":"Overlooked histories in ageing research: Pioneering women at the foundation of our field","authors":"Marina Ezcurra, Colin Selman, Jennifer Tullet, Nathan Woodling","doi":"10.1111/acel.14432","DOIUrl":"10.1111/acel.14432","url":null,"abstract":"A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer ‘history of the field’ that many of us present in our classrooms, conference halls and writings often tends to be dominated by men. Although numerous men have made fundamental observations that have shaped our understanding of ageing from both a mechanistic and evolutionary perspective, the unfortunate reality is that women making similar contributions have not received equal recognition throughout much of our field's history. As a starting point for wider representation and further conversations in this area, we present here a short list of women—Marjory Warren, Lillian Jane Martin, Margaret Alexander Ohlson, Rebeca Gerschman and Marion J. Lamb—whose contributions were foundational to ageing research in the 20th century. Their work spanned theoretical, experimental and clinical insight into the biology of ageing—and yet their names are too seldom mentioned when introducing our field. We hope this list can be a starting point for a more inclusive recognition of the diverse scientists who helped pave the way for our field today.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737961","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

Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats 下调RUVBL2可改善hnRNPA2/ b1应激颗粒动态，抑制老年轻度认知障碍大鼠围手术期神经认知障碍。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-28 DOI: 10.1111/acel.14418

Zixuan Wang, Chenyi Yang, Xinyi Wang, Huihui Liao, Xing Liu, Huan Liu, Miao Zhang, Lin Zhang, Haiyun Wang

{"title":"Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats","authors":"Zixuan Wang, Chenyi Yang, Xinyi Wang, Huihui Liao, Xing Liu, Huan Liu, Miao Zhang, Lin Zhang, Haiyun Wang","doi":"10.1111/acel.14418","DOIUrl":"10.1111/acel.14418","url":null,"abstract":"Perioperative neurocognitive disorders (PND) is common in aged mild cognitive impairment (MCI) patients and can accelerate the progression to dementia. This process involves heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1)-mediated aggregates of stress granules (SGs), while RUVBL2 influences the dynamics of these SGs. Our research explored a new target for modulating hnRNAPA2/B1-SGs dynamics to accelerate their disassembly and potentially delay MCI progression due to PND. We assessed the effect of hippocampal RUVBL2 knockdown on hnRNPA2/B1-SGs in aged MCI rats through behavioral studies, biochemical experiments and MRI. We also examined hnRNPA2/B1-SGs dynamics using immunofluorescence staining and fluorescence recovery after photobleaching (FRAP) in rat primary hippocampal neurons. Our results revealed that hnRNPA2/B1 in the hippocampus of aged MCI rats translocates to the cytoplasm to form SGs following anesthesia. RUVBL2 knockdown promotes the disappearance of hnRNPA2/B1-SGs, allowing hnRNPA2/B1 to return to the nucleus and enhancing functional activity in the brain regions of aged MCI rats. In primary hippocampal neurons, RUVBL2 deletion facilitated hnRNPA2/B1-SGs transition from hydrogel to liquid, promoting disassembly. We compared three commonly used general anesthetics—3% sevoflurane, 40 mg·kg−1·h−1 propofol, and 9% desflurane. Sevoflurane upregulated RUVBL2, which decreased the intraneuronal pH and disrupted energy metabolism. These changes resulted in greater stabilization of hnRNPA2/B1- SGs. In conclusion, our findings indicated that the knockdown of RUVBL2 expression contributes to the transition of hnRNPA2/B1-SGs from the hydrogel phase to the liquid phase. Targeted interference with RUVBL2 may represent a novel approach to delay the progression to dementia due to PND in aged MCI patients.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749388","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 Ercc1−/Δ mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration Ercc1-/Δ XFE早衰综合征小鼠模型会加速视网膜退化。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-27 DOI: 10.1111/acel.14419

Akilavalli Narasimhan, Seok Hong Min, Laura L. Johnson, Heidi Roehrich, William Cho, Tracy K. Her, Caeden Windschitl, Ryan D. O'Kelly, Luise Angelini, Matthew J. Yousefzadeh, Linda K. McLoon, William W. Hauswirth, Paul D. Robbins, Dorota Skowronska-Krawczyk, Laura J. Niedernhofer

{"title":"The Ercc1−/Δ mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration","authors":"Akilavalli Narasimhan, Seok Hong Min, Laura L. Johnson, Heidi Roehrich, William Cho, Tracy K. Her, Caeden Windschitl, Ryan D. O'Kelly, Luise Angelini, Matthew J. Yousefzadeh, Linda K. McLoon, William W. Hauswirth, Paul D. Robbins, Dorota Skowronska-Krawczyk, Laura J. Niedernhofer","doi":"10.1111/acel.14419","DOIUrl":"10.1111/acel.14419","url":null,"abstract":"Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related retinal changes. To address this, we used a genetic model of systemic depletion of expression of the DNA repair enzyme ERCC1-XPF. The neural retina and retinal pigment epithelium (RPE) from Ercc1−/Δ mice, which models a human progeroid syndrome, were compared to age-matched wild-type (WT) and old WT mice. By 3-months-of age, Ercc1−/Δ mice presented abnormal optokinetic and electroretinogram responses consistent with photoreceptor dysfunction and visual impairment. Ercc1−/Δ mice shared many ocular characteristics with old WT mice including morphological changes, elevated DNA damage markers (γ-H2AX and 53BP1), and increased cellular senescence in the neural retinal and RPE, as well as pathological angiogenesis. The RPE is essential for the metabolic health of photoreceptors. The RPE from Ercc1−/Δ mice displayed mitochondrial dysfunction causing a compensatory glycolytic shift, a characteristic feature of aging RPE. Hence, our study suggests spontaneous endogenous DNA damage promotes the hallmarks of age-related retinal degeneration.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737962","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}

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