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Advances in the Regulation by Immune Cells of Skeletal Myositis Outcomes. 免疫细胞调控骨骼肌炎预后的研究进展。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-17 DOI: 10.14336/AD.2025.0549
Shuxian Huang, Yongling Zhao, Yuanpeng Xin, Ziqi Yao, Yi Deng, Qihui Cai, Junyi Xie, Ruixue Wang, Zhaohong Liao
{"title":"Advances in the Regulation by Immune Cells of Skeletal Myositis Outcomes.","authors":"Shuxian Huang, Yongling Zhao, Yuanpeng Xin, Ziqi Yao, Yi Deng, Qihui Cai, Junyi Xie, Ruixue Wang, Zhaohong Liao","doi":"10.14336/AD.2025.0549","DOIUrl":"https://doi.org/10.14336/AD.2025.0549","url":null,"abstract":"<p><p>Skeletal myositis prevalence is increasing annually, impairing mobility and potentially causing acute organ failure. Following muscle injury, various factors within damaged muscle trigger immune cell exudation from the bloodstream to the injured area, influencing disease progression. This paper synthesizes global research on cellular/molecular mechanisms in skeletal myositis, examining immune cell regulation in exogenous-induced skeletal myositis, dystrophic myopathy, and idiopathic inflammatory myopathy (IIM). We conclude that cytokines from intramuscular immune cells represent key targets for clinical management and therapeutic development.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Cognitive Functions Dementia Battery: A Novel Computerized Tool for Neurocognitive Disorders. 认知功能痴呆电池:一种新的神经认知障碍计算机化工具。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-17 DOI: 10.14336/AD.2025.0412
Raquel Lemos, Sofia Areias-Marques, Alexandros Lazaridis, Johanna Zils, Cristina Martins, Sílvia Almeida, Luísa Alves, David Brieber, Albino J Oliveira-Maia
{"title":"The Cognitive Functions Dementia Battery: A Novel Computerized Tool for Neurocognitive Disorders.","authors":"Raquel Lemos, Sofia Areias-Marques, Alexandros Lazaridis, Johanna Zils, Cristina Martins, Sílvia Almeida, Luísa Alves, David Brieber, Albino J Oliveira-Maia","doi":"10.14336/AD.2025.0412","DOIUrl":"https://doi.org/10.14336/AD.2025.0412","url":null,"abstract":"<p><p>The Cognitive Functions Dementia (CFD) is a computerized battery to assess the cognitive domains included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for neurocognitive disorders. We aimed at examining the psychometric properties and the clinical validity of the CFD for neurocognitive disorders. Psychometric characterization was conducted in healthy individuals, stratified according to age, sex, and education to represent a norming sample. Analyses included structural validity and measurement invariance, assessed through confirmatory factor analyses (CFA) and multi-group CFA, as well as internal consistency, and re-test reliability of the battery index values. Patients with major or minor neurocognitive disorder contributed data to compute receiver operating characteristics to assess diagnostic accuracy of the CFD indices relative to healthy participants. Data from 422 healthy volunteers and 81 patients were collected for the study. The confirmatory factor analysis model confirmed the validity of the structure proposed for CFD, with the five cognitive domains (attention, verbal long-term memory, expressive language, executive functions, and perceptual motor functions) describing an overall factor (CFD-Index). Good to excellent values of internal consistency and of re-test reliability were obtained for all indices. Importantly, CFD indexes were accurate in discriminating patients with neurocognitive disorders from healthy participants. The CFD battery is a valid and reliable computerized instrument to characterize patients with neurocognitive dysfunction.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Age-, sex-, and ancestry-specific prevalence of hearing loss in UK Biobank and All of Us Research Program. 英国生物银行和我们所有人研究项目中听力损失的年龄、性别和血统特异性患病率。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-16 DOI: 10.14336/AD.2025.0754
Jun He, Sharon G Curhan, Gary C Curhan, Renato Polimanti
{"title":"Age-, sex-, and ancestry-specific prevalence of hearing loss in UK Biobank and All of Us Research Program.","authors":"Jun He, Sharon G Curhan, Gary C Curhan, Renato Polimanti","doi":"10.14336/AD.2025.0754","DOIUrl":"10.14336/AD.2025.0754","url":null,"abstract":"<p><p>Hearing loss (HL) is a leading cause of global disease burden, but limited information is available regarding differences among individuals of diverse ancestral backgrounds. Here, we assessed age-, sex-, and ancestry-specific prevalence of HL in 827 406 participants from UK Biobank (UKB, N = 448 193) and All of Us Research Program (AoU, N = 379 213). HL was defined based on electronic health records and self-reported information, and HL prevalence was calculated for each subgroup. Age trends and prevalence differences between sexes and ancestries were tested. Age-standardized prevalence was computed for UKB and AoU using the combined sample size of the two cohorts as the standard population. The overall HL prevalence was 28% in UKB (24% in females; 34% in males) and 16% in AoU (13% in females; 20% in males). Sex differences were statistically significant across all age groups in UKB, and among participants aged &;gt55 years in AoU. Across ancestry groups, males had a higher prevalence of HL than females, except for those of African descent in the AoU sample (10% in females and 9.5% in males). The ancestry-specific prevalence was highest among those of European descent in both UKB (29%) and AoU (20%), and lowest among those of African descent (12%) in UKB and Central/South Asian descent (7.3%) in AoU. The HL polygenic risk score was associated with HL in both female and male samples. Overall, this study provides comprehensive evidence that sex differences in HL prevalence should be considered in the context of population diversity.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
VCAM-1 in Cognitive Impairment: Mechanisms, Biomarker Potential, and Therapeutic Targeting. 认知障碍中的VCAM-1:机制、生物标志物潜力和治疗靶向。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-11 DOI: 10.14336/AD.2025.0675
Xilong Guan, Xiaoling Zhu, Linan Zha, Wen Yu, Xiuqin Rao, Yanhong Xiong, Yu Jin, Mojiao Zhang, Tao Luo, Xiangfei Huang, Xifeng Wang, Fuzhou Hua, Jing Xu
{"title":"VCAM-1 in Cognitive Impairment: Mechanisms, Biomarker Potential, and Therapeutic Targeting.","authors":"Xilong Guan, Xiaoling Zhu, Linan Zha, Wen Yu, Xiuqin Rao, Yanhong Xiong, Yu Jin, Mojiao Zhang, Tao Luo, Xiangfei Huang, Xifeng Wang, Fuzhou Hua, Jing Xu","doi":"10.14336/AD.2025.0675","DOIUrl":"https://doi.org/10.14336/AD.2025.0675","url":null,"abstract":"<p><p>Cognitive impairment (CI), a progressive decline in memory, reasoning, and executive functions, arises from neurodegenerative and cerebrovascular pathologies. Globally, 10% of adults aged ≥65 exhibit mild CI (MCI), with 15% progressing annually to dementia. Alzheimer's disease (AD) constitutes 60-70% of dementia cases, showing a higher incidence in women, while vascular dementia (VaD) accounts for 20%. By 2050, dementia cases may reach 152 million, straining healthcare systems. Vascular cell adhesion molecule 1 (VCAM-1), a key immune-inflammatory mediator, is implicated in CI pathogenesis. Expressed abundantly on endothelial cells, VCAM-1 disrupts blood-brain barrier (BBB) integrity and exacerbates neuroinflammation. This review delineates VCAM-1's role in BBB dysregulation, neuroinflammatory interactions, and its potential as a biomarker/therapeutic target. Future research should clarify VCAM-1 signaling mechanisms and develop targeted interventions for early CI management.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Cardiovascular Health, as per Life's Essential 8, and Impaired Lower-Extremity Function in Older Adults. 心血管健康,根据生活的基本8,和老年人的下肢功能受损。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-11 DOI: 10.14336/AD.2025.0347
David Gómez-Ángel, Mercedes Sotos-Prieto, David Martínez-Gómez, Auxiliadora Graciani, Esther García-Esquinas, Fernando Rodríguez-Artalejo, Rosario Ortolá
{"title":"Cardiovascular Health, as per Life's Essential 8, and Impaired Lower-Extremity Function in Older Adults.","authors":"David Gómez-Ángel, Mercedes Sotos-Prieto, David Martínez-Gómez, Auxiliadora Graciani, Esther García-Esquinas, Fernando Rodríguez-Artalejo, Rosario Ortolá","doi":"10.14336/AD.2025.0347","DOIUrl":"https://doi.org/10.14336/AD.2025.0347","url":null,"abstract":"<p><p>Cardiovascular health (CVH) is a broad construct that encompasses multiple behavioral and biological factors. A decline in CVH has been associated with various adverse health outcomes, but its role in impaired lower-extremity function (ILEF), a major contributor to disability, diminished quality of life and mortality in older adults, is unknown. Therefore, we examined the cross-sectional and prospective association between CVH and lower-extremity function. Using data from 2,487 individuals aged ≥65y from the Seniors-ENRICA-2 cohort, we estimated CVH at baseline using the American Heart Association's Life's Essential 8 (LE8) score (range 0 to 100, with higher values indicating better CVH). We assessed ILEF at baseline and at 2.4-year and 5.2-year follow-ups using the Short Physical Performance Battery (SPPB). Statistical analyses were conducted with logistic regression with adjustment for the main confounders. ILEF was present in 26.8% of participants at baseline (666 events). The cumulative incidence over 2.4 and 5.2 years was 24.8% (278 events) and 22.5% (157 events), respectively. A 10-point higher LE8 score at baseline was associated with lower prevalence of ILEF (SPPB ≤9) at baseline (odds ratio [OR] 0.75, 95% confidence interval [CI]: 0.69-0.80), and lower risk of incident ILEF over 2.4 years (OR 0.77, 95% CI: 0.68-0.87) and 5.2 years (OR 0.76, 95% CI: 0.65-0.89). Physical activity, glucose levels, body mass index and nicotine exposure stood out as major contributors to the lower risk of incident ILEF associated with a higher LE8 score. A higher LE8 score was associated with both a lower prevalence and incidence of ILEF in older adults. Comprehensive evaluation of CVH offers insight into older adults' lower-extremity function and how it may progress over time, identifying opportunities for early intervention.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Spinal Cord Injury and Ageing: The Role of Chronic Neuroinflammation. 脊髓损伤与衰老:慢性神经炎症的作用。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-07 DOI: 10.14336/AD.2025.10630
Tianwei Wang, Zhaoyang Zhang, Jian Liu, Liping Zhang, Qingbin Ni, Baoliang Sun, Jingyi Sun
{"title":"Spinal Cord Injury and Ageing: The Role of Chronic Neuroinflammation.","authors":"Tianwei Wang, Zhaoyang Zhang, Jian Liu, Liping Zhang, Qingbin Ni, Baoliang Sun, Jingyi Sun","doi":"10.14336/AD.2025.10630","DOIUrl":"https://doi.org/10.14336/AD.2025.10630","url":null,"abstract":"<p><p>As the global population ages, there is an increasing prevalence of spinal cord injury (SCI) among elderly individuals, accompanied by significant challenges in treatment and recovery. Age-related conditions, such as osteoporosis, muscle atrophy, and impaired balance, predispose older adults to falls and traumatic injuries, leading to worse neurological outcomes compared to younger patients. SCI pathophysiology consists of two phases: the initial mechanical injury and the secondary injury that involves a cascade of pathological events, including ischemia, apoptosis, and neuronal cell death. Chronic neuroinflammation has emerged as a central factor in driving long-term damage after SCI, particularly in older people, where immune senescence and a decreased ability to resolve inflammation contribute to persistent, unresolved inflammation. This prolonged inflammatory state further impedes neural regeneration and functional recovery. Aged animal models have revealed that chronic neuroinflammation is exacerbated by sustained activation of microglia and astrocytes, the infiltration of peripheral immune cells, and the secretion of pro-inflammatory cytokines, creating a pro-inflammatory microenvironment that hinders repair. Furthermore, ageing-related factors such as immunosenescence, autophagy dysfunction, and mitochondrial abnormalities exacerbate inflammation, establishing a vicious injury cycle. Despite promising studies targeting inflammation in young SCI models, there is a critical need for age-specific therapeutic approaches for elderly SCI patients. This review explores the mechanisms of chronic inflammation in aged SCI, examines key cellular mediators, and discusses potential therapeutic strategies, including pharmacological treatments, gene therapy, exosome-based interventions, and rehabilitation. Focusing on age-related differences in inflammation and healing, this work aims to provide a foundation for precision medicine tailored to the ageing population with SCI, ultimately improving clinical outcomes and quality of life for elderly patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism. 帕金森病代谢失调:非氧化磷酸化及其在脑能量代谢中的作用
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-06 DOI: 10.14336/AD.2025.0619
Marta Pokotylo, Norbert Brüggemann, Jannik Prasuhn
{"title":"Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.","authors":"Marta Pokotylo, Norbert Brüggemann, Jannik Prasuhn","doi":"10.14336/AD.2025.0619","DOIUrl":"https://doi.org/10.14336/AD.2025.0619","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative condition affecting around 1-2% of the population over the age of 60. The lack of disease-modifying therapies highlights the need for insights into the etiology and pathogenesis of PD. Mitochondrial dysfunction is recognized to be a significant contributor to disease pathogenesis, resulting in bioenergetic deficits and subsequent neurodegeneration. Research indicates that changes in non-oxidative phosphorylation (non-OXPHOS) metabolism in PD may serve as an adaptive response to mitochondrial dysfunction, compensating for energetic failure and alleviating disease progression. This review explores mitochondrial dysfunction-driven alterations in non-OXPHOS metabolic pathways, such as glycolysis and the tricarboxylic acid cycle, emphasizing their role in maintaining energy metabolism and their dual contribution to neuroprotection and disease progression. Advances in neuroimaging techniques are also discussed, particularly their role in visualizing metabolic changes in vivo and their potential utility in identifying non-OXPHOS metabolism as a biomarker of mitochondrial dysfunction. By enhancing our understanding of the complex interplay between metabolic pathways in PD, this review underscores the importance of personalized therapeutic approaches that consider individual metabolic variations. Ultimately, these insights aim to pave the way for improved diagnostic utility and personalized treatment strategies that address the metabolic and mitochondrial dysfunctions underlying PD pathogenesis.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Adaptive Immune Dyshomeostasis as a Mediator of Vascular Cognitive Decline: Unraveling Neurovascular Crosstalk. 适应性免疫平衡失调是血管认知衰退的中介:解开神经血管串扰。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-04 DOI: 10.14336/AD.2025.0380
Yating Li, Jinlin Shen, Li Zhang, Yang Luo
{"title":"Adaptive Immune Dyshomeostasis as a Mediator of Vascular Cognitive Decline: Unraveling Neurovascular Crosstalk.","authors":"Yating Li, Jinlin Shen, Li Zhang, Yang Luo","doi":"10.14336/AD.2025.0380","DOIUrl":"https://doi.org/10.14336/AD.2025.0380","url":null,"abstract":"<p><p>Vascular cognitive impairment and dementia (VCID), the second most prevalent form of dementia worldwide, arises from cerebrovascular injury and is increasingly recognized as an immune-mediated neurovascular disorder. Mounting evidence implicates dysregulated immune responses-both central and peripheral-as critical drivers of VCID pathogenesis. This review highlights the pivotal roles of microglial activation, astrocytic reactivity, and infiltration of pro-inflammatory T and B cells in disrupting the neurovascular unit (NVU). These processes, mediated by cytokines such as IL-6, IL-17A, and IFN-γ, contribute to the blood-brain barrier (BBB) breakdown, white matter degeneration, and neuronal dysfunction. We further examine how systemic inflammation and comorbidities including hypertension, diabetes, and gut dysbiosis exacerbate immune-neurovascular crosstalk. In light of these insights, we discuss emerging therapeutic strategies aimed at modulating neuroimmune interactions and restoring neurovascular integrity. This integrated perspective provides a foundation for developing precise, immune-targeted interventions in the prevention and treatment of VCID.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 GFAP and Amyloid Pathology Predict Cognitive Response to Multidomain Interventions in MCI. 血浆GFAP和淀粉样蛋白病理学预测MCI患者对多域干预的认知反应。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-04 DOI: 10.14336/AD.2025.0646
Myung-Hoon Han, Mina Hwang, Hyuk Sung Kwon, So Young Moon, Yoo Kyoung Park, Jee Hyang Jeong, Seong Hye Choi, Seong-Ho Koh
{"title":"Plasma GFAP and Amyloid Pathology Predict Cognitive Response to Multidomain Interventions in MCI.","authors":"Myung-Hoon Han, Mina Hwang, Hyuk Sung Kwon, So Young Moon, Yoo Kyoung Park, Jee Hyang Jeong, Seong Hye Choi, Seong-Ho Koh","doi":"10.14336/AD.2025.0646","DOIUrl":"https://doi.org/10.14336/AD.2025.0646","url":null,"abstract":"<p><p>There is limited evidence on which biological markers can predict the effectiveness of interventions in mild cognitive impairment (MCI) patients, particularly in relation to amyloid pathology. This study aims to investigate whether plasma glial fibrillary acidic protein (GFAP) levels can serve as a predictive biomarker for short-term cognitive response to multidomain interventions in elderly individuals with MCI, stratified by probable amyloid-β plaque deposition. In this 24-week multicenter randomized controlled trial (RCT; SUPERBRAIN-MEET), 300 elderly participants with MCI were enrolled. Probable amyloid status was determined using a plasma phosphorylated tau 181 cutoffs derived from a validated cohort. Multivariable linear regression analyses were employed to assess the association between plasma GFAP levels and percentage changes in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores, stratified by amyloid deposition status and intervention group. Higher plasma GFAP levels at baseline and 6 months were independently and significantly associated with smaller percentage improvements in RBANS scores over 6 months. Among participants with probable amyloid positivity who underwent the multidomain intervention, increased baseline GFAP levels were significantly associated with reduced cognitive improvement compared to those with lower levels (β = -8.661, p = 0.040). This post hoc exploratory subanalysis, based on data from a multicenter RCT, suggests that plasma GFAP may serve as a biomarker for early cognitive stage transitions in elderly individuals with MCI. Baseline GFAP levels-particularly among those with probable amyloid pathology-may help predict cognitive responsiveness to multidomain interventions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Lars2 Deficiency-Induced Mitochondrial Dysfunction Drives the Emergence of a Pro-Inflammatory Stroke-Specific Microglial Subpopulation. Lars2缺陷诱导的线粒体功能障碍驱动促炎卒中特异性小胶质细胞亚群的出现。
IF 7 2区 医学
Aging and Disease Pub Date : 2025-07-04 DOI: 10.14336/AD.2025.0387
Qing Zou, Jianxin Zhou, Ying Li, Jiaming Shi, Jingying Huang, Cheng Zhuang, Hao Wu, Huanle Hong, Yanan Guo, Qian Li, Robert Chunhua Zhao, Jiao Wang
{"title":"Lars2 Deficiency-Induced Mitochondrial Dysfunction Drives the Emergence of a Pro-Inflammatory Stroke-Specific Microglial Subpopulation.","authors":"Qing Zou, Jianxin Zhou, Ying Li, Jiaming Shi, Jingying Huang, Cheng Zhuang, Hao Wu, Huanle Hong, Yanan Guo, Qian Li, Robert Chunhua Zhao, Jiao Wang","doi":"10.14336/AD.2025.0387","DOIUrl":"https://doi.org/10.14336/AD.2025.0387","url":null,"abstract":"<p><p>Stroke significantly alters microglial immune status beyond the traditional M1/M2 classification. We analyzed single-cell RNA sequencing data from the striatum of hemorrhagic, ischemic, and control mice, revealing activation of mitochondrial autophagy and assembly processes after stroke. Gene Ontology functional enrichment analysis indicated that stroke-associated genes predominantly regulate mitochondrial maintenance, with leucyl-tRNA synthetase 2 (Lars2) markedly upregulated in post-stroke microglia. A distinct microglial subset (Mc) was identified with notably low Lars2 expression. In vitro, Lars2 overexpression enhanced mitochondrial function, reduced pro-inflammatory cytokine release, and suppressed Mc marker gene expression. Cell-cell communication analysis revealed Mc as the most interactive microglial subset following stroke, particularly engaging with neurons. Among neuron-Mc signaling pairs, the neurotrophic factor pleiotrophin-syndecan-4 (PTN-SDC4) ligand-receptor pair emerged as a key mediator. Conditioned media from stressed microglia upregulated neuronal Ptn expression, likely recruiting microglia, as exogenous PTN promoted microglial migration. These findings identify Mc as a stroke-induced microglial population with low Lars2 expression and pro-inflammatory features. The lack of compensatory mitochondrial repair in Mc contributes to pro-inflammatory polarization, positioning Lars2 as a mitochondrial checkpoint linking stroke-induced microglial reprogramming to neuroinflammation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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