Aging and Disease最新文献_第5页

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":"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.","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":"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.","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":"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.","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

GABA Levels Are Significantly Reduced in the Visual, Motor, and Auditory Cortex of Patients with Mild Cognitive Impairment. 轻度认知障碍患者的视觉、运动和听觉皮层中GABA水平显著降低。

IF 7 2区医学

Aging and Disease Pub Date : 2025-07-03 DOI: 10.14336/AD.2025.0334

Mark D Zuppichini, Abbey M Hamlin, Quan Zhou, Esther Kim, Kayla Wyatt, Noah Reardon, Benjamin M Hampstead, Thad A Polk

{"title":"GABA Levels Are Significantly Reduced in the Visual, Motor, and Auditory Cortex of Patients with Mild Cognitive Impairment.","authors":"Mark D Zuppichini, Abbey M Hamlin, Quan Zhou, Esther Kim, Kayla Wyatt, Noah Reardon, Benjamin M Hampstead, Thad A Polk","doi":"10.14336/AD.2025.0334","DOIUrl":"https://doi.org/10.14336/AD.2025.0334","url":null,"abstract":"One factor that might contribute to functional deterioration in patients with mild cognitive impairment (pwMCI) is a reduction in the brain's major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Previous studies have reported reductions in GABA in pwMCI while others have not. Here we use magnetic resonance spectroscopy (MRS) to estimate GABA + macromolecules due to co-editing (GABA+) levels in six different brain regions in 37 pwMCI and 163 healthy controls. We estimate GABA+ levels using both creatine and water as reference molecules, and we analyze the effect of correcting for grey matter volume. When referenced to water, we found that GABA+ was significantly lower in pwMCI compared to controls in all six regions, even after tissue composition correction. When referenced to creatine, all but two regions exhibited lower amounts of GABA+ for pwMCI, even after controlling for tissue composition. Results suggest that pwMCI experience reductions in GABA+ throughout the brain, even in regions not typically associated with cognitive impairment.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666793","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 Complex Bidirectional Relationship Between Aging and Atherosclerosis: Mechanistic Insights and Translational Opportunities. 衰老与动脉粥样硬化之间复杂的双向关系：机制见解和转化机会。

IF 7 2区医学

Aging and Disease Pub Date : 2025-07-02 DOI: 10.14336/AD.2025.10620

Binquan You, Dong Yi, Bingyin Wang, Hua Yan

引用次数: 0

Mechanistic Role of Astrocytic Rac1 Protein in Alzheimer's Disease. 星形细胞Rac1蛋白在阿尔茨海默病中的机制作用。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-28 DOI: 10.14336/AD.2025.0502

Fengwen Jiang, Niya Wang, Qiang Meng

引用次数: 0

Regulatory and Influencing Factors of Digestive Function in Elderly People: Roles of the Gut Microbiota and Nutritional Interventions. 老年人消化功能的调节和影响因素：肠道菌群的作用和营养干预。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-27 DOI: 10.14336/AD.2025.0565

Ka Li, Safia Arbab, Qiujing Du, Jiao Zhou, Yuwen Chen, Yali Tian, Li Qijie, Hanif Ullah, Ben Zhang

{"title":"Regulatory and Influencing Factors of Digestive Function in Elderly People: Roles of the Gut Microbiota and Nutritional Interventions.","authors":"Ka Li, Safia Arbab, Qiujing Du, Jiao Zhou, Yuwen Chen, Yali Tian, Li Qijie, Hanif Ullah, Ben Zhang","doi":"10.14336/AD.2025.0565","DOIUrl":"https://doi.org/10.14336/AD.2025.0565","url":null,"abstract":"Aging is a natural and gradual biological process through which living organisms undergo physical, physiological, and sometimes psychological changes over time. Aging is commonly associated with a decline in gastrointestinal function, leading to various digestive disorders that impact the quality of life of older adults. The gut microbiota is a highly complex ecosystem that plays crucial roles in digestion, metabolic processes, immune functions, and overall health. However, emerging evidence indicates that many elderly individuals maintain relatively stable digestive health, suggesting the influence of modifiable regulatory factors. In this review, we describe the key physiological, microbial, and nutritional factors that regulate and influence digestive function in an aging population. Additionally, we explored the impact of age-associated alterations in the gut microbiota on digestive health challenges in older adults and emphasized the therapeutic potential of targeted nutritional intervention approaches, such as dietary modifications, prebiotics, probiotics, and symbiotic and fecal microbiota transplantation, which have shown promise in rebalancing the gut microbiome and reducing inflammation.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525985","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

Unveiling the Relation between Cellular Ageing, Epigenetics and Cancer. 揭示细胞衰老、表观遗传学和癌症之间的关系。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-27 DOI: 10.14336/AD.2025.0677

Pawel Kordowitzki, Arkadiusz Grzeczka

{"title":"Unveiling the Relation between Cellular Ageing, Epigenetics and Cancer.","authors":"Pawel Kordowitzki, Arkadiusz Grzeczka","doi":"10.14336/AD.2025.0677","DOIUrl":"https://doi.org/10.14336/AD.2025.0677","url":null,"abstract":"This Editorial article intends to unravel the relationships among cellular ageing, epigenetic changes, and tumorigenesis, thereby offering perspectives that could improve therapeutic approaches in cancer management and promote future research on these topics. Furthermore, selected fundamental principles concerning cellular ageing will be presented to elucidate how this process contributes to the comprehension of tumorigenesis. As humans age, there is a progressive decline in physiological functions, which significantly increases the risk of cancer. Epigenetic alterations-heritable yet reversible modifications of the genome without changes in DNA sequence-play a pivotal role in both ageing and tumorigenesis. Age-associated epigenetic drift, involving widespread DNA methylation changes, histone modification shifts, and chromatin remodelling, disrupts normal gene regulatory networks, leading to genomic instability and impaired cellular homeostasis. Additionally, the accumulation of senescent cells, driven by epigenetic dysregulation, fosters a pro-inflammatory environment that can promote tumorigenesis. Moreover, the epigenetic landscape of aged tissues resembles that of cancerous tissues, suggesting that ageing establishes a permissive environment for malignant transformation. Understanding the interplay between ageing, epigenetic regulation, and cancer is critical for the development of preventive strategies and novel therapeutics. Epigenetic reprogramming technologies, aiming to restore youthful epigenetic states, hold promise for delaying ageing and reducing cancer incidence. However, challenges remain in selectively targeting pathogenic epigenetic changes without disrupting essential cellular functions.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525990","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

Recent Advances in Aging-Related Diseases: Accelerated Aging, Molecular Mechanisms, Interventions, and Therapies. 衰老相关疾病的最新进展：加速衰老、分子机制、干预和治疗。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-26 DOI: 10.14336/AD.2025.10618

Elham Sadat Afraz, Seyed Alireza Hoseinikhah, Nasrollah Moradikor

{"title":"Recent Advances in Aging-Related Diseases: Accelerated Aging, Molecular Mechanisms, Interventions, and Therapies.","authors":"Elham Sadat Afraz, Seyed Alireza Hoseinikhah, Nasrollah Moradikor","doi":"10.14336/AD.2025.10618","DOIUrl":"10.14336/AD.2025.10618","url":null,"abstract":"Aging is a multifaceted biological process influenced by cellular stress, mitochondrial dysfunction, and immune system alterations. This editorial commentary categorizes recent findings of Aging and Disease into three main areas: the acceleration of aging, prediction of age-related decline, and emerging therapeutic strategies. Research indicates that factors such as oxidative stress, chronic inflammation, and genetic predispositions contribute to premature cellular aging and the onset of age-related diseases. Recent advances in biomarkers and machine learning have improved our ability to predict biological age and associated risks, including sarcopenia and cardiovascular decline. Promising therapeutic interventions such as mitochondrial transplantation, immune system modulation, and targeted gene therapies show efficacy in decelerating aging processes and treating conditions such as Alzheimer's disease and tissue fibrosis. A deeper understanding of these interconnected mechanisms lays the groundwork for developing personalized interventions that promote healthy aging.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":"16 4","pages":"1785-1792"},"PeriodicalIF":7.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities. 炎症小体- mir轴在阿尔茨海默病和慢性疼痛中的作用：分子机制和治疗机会。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-25 DOI: 10.14336/AD.2025.0353

Botond Gaál, Roland Takács, Csaba Matta, Krisztián Juhász, Béla Fülesdi, Zoltán Szekanecz, Szilvia Benkő, László Ducza

{"title":"The Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities.","authors":"Botond Gaál, Roland Takács, Csaba Matta, Krisztián Juhász, Béla Fülesdi, Zoltán Szekanecz, Szilvia Benkő, László Ducza","doi":"10.14336/AD.2025.0353","DOIUrl":"https://doi.org/10.14336/AD.2025.0353","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and chronic neuroinflammation. Mounting evidence suggests that inflammasome activation plays a pivotal role in the onset and progression of AD by promoting neuronal damage, Tau pathology, and amyloid-β (Aβ) accumulation. Among the various inflammasome types expressed in the central nervous system (CNS), NLRP3 has received particular attention due to its strong association with both AD and pain-related neuroinflammation. Chronic pain, frequently observed in older adults and individuals with dementia, shares overlapping inflammatory mechanisms with AD, including glial activation and cytokine dysregulation. The inflammasome-microRNA (miR) axis has recently emerged as a key regulatory pathway modulating these neuroinflammatory responses. Specific inflammation-associated miRs, such as miR-22, miR-34a, miR-146a, miR-155, and miR-223, influence innate immune signaling and critically affect both neuronal homeostasis and pain sensitization. Emerging evidence also implicates dysfunction of the locus coeruleus-noradrenergic (LC-NE) system-an early target of AD pathology-in amplifying neuroinflammation and pain sensitivity, partly through interactions with dysregulated miRs. While previous studies have addressed the roles of inflamma-miRs in AD or chronic pain individually, this review uniquely examines their interconnected roles-highlighting how dysregulated miR expression and inflammasome activation may converge to drive persistent neuroinflammation across both conditions. By elucidating shared molecular pathways, we propose that targeting the inflammasome-miR axis may offer dual therapeutic potential: slowing AD progression while addressing pain-related neural dysfunction. As the prevalence of AD rises, such integrated insights are essential for the development of more precise, mechanism-based interventions.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525989","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