Ageing Research Reviews最新文献_第6页

Meta-analyses of personality change from the preclinical to the clinical stages of dementia 痴呆症临床前到临床阶段人格改变的meta分析。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-08-05 DOI: 10.1016/j.arr.2025.102852

Antonio Terracciano , Martina Luchetti , Selin Karakose , Amanda A. Miller , Yannick Stephan , Angelina R. Sutin

{"title":"Meta-analyses of personality change from the preclinical to the clinical stages of dementia","authors":"Antonio Terracciano , Martina Luchetti , Selin Karakose , Amanda A. Miller , Yannick Stephan , Angelina R. Sutin","doi":"10.1016/j.arr.2025.102852","DOIUrl":"10.1016/j.arr.2025.102852","url":null,"abstract":"<div><div>Personality changes are a clinical criterion for dementia diagnosis, yet their progression across disease stages remains unclear. This systematic review and meta-analyses examined change in the five major personality traits across the preclinical, transitional, and clinical dementia stages. We conducted pre-registered searches of three databases from their inception to November 2024. The standardized mean difference (SMD) with 95 % CIs were combined in random-effects meta-analyses. Prospective studies based on self-reports of personality (13 studies; N = 6895) found subtle changes in the preclinical and transitional stages (SMD = 0–0.2), which became more pronounced (SMD = 0.3–0.5) in the clinical stage. Retrospective studies based on informant ratings (26 studies; N = 1069) found smaller changes during mild cognitive impairment compared to dementia, with large (>1 SMD) increases in neuroticism and decreases in extraversion and conscientiousness. Surprisingly, changes in frontotemporal dementia were slightly smaller than those observed in Alzheimer’s disease. By triangulating findings across study designs, we conclude that personality changes are subtle and inconsistent in the early preclinical stage. Personality changes become significant and pronounced as the disease progresses, in line with the rise of emotional and behavioral symptoms. Future multimethod studies should examine to what extent the rate of change is related to the underlying neurodegenerative processes. Our findings provide a framework for interpreting the timing and magnitude of non-cognitive changes in dementia, informing disease monitoring and targeted symptom management.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102852"},"PeriodicalIF":12.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769365","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

Beyond the 900-day rule: Reclaiming healthspan as geroscience’s primary goal 超越900天规则：恢复健康寿命是老年科学的首要目标

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-08-05 DOI: 10.1016/j.arr.2025.102857

Stef F. Verlinden

{"title":"Beyond the 900-day rule: Reclaiming healthspan as geroscience’s primary goal","authors":"Stef F. Verlinden","doi":"10.1016/j.arr.2025.102857","DOIUrl":"10.1016/j.arr.2025.102857","url":null,"abstract":"<div><div>The recently proposed “900-day rule” in mouse aging studies—requiring lifespan extension over ultra-long-lived controls—aims to identify interventions that modulate intrinsic aging. While this standard raises scientific rigor, it may reduce relevance to how most organisms, including humans, actually age. In reality, aging unfolds under metabolically and immunologically stressful conditions—not in sterile, genetically uniform environments. Most people experience chronic inflammation, metabolic drift, and functional decline long before death. Prioritizing only pristine models risks overlooking the hallmarks of manifest aging: frailty, cognitive loss, immune erosion. This Viewpoint argues for a dual-track strategy: rigorous lifespan testing in ideal models should be complemented by phenotype-driven studies in real-world aging models—such as conventionally housed mice in academic settings—that reflect typical aging trajectories. Interventions like GlyNAC, NLRP3 inhibition, and CaAKG demonstrate broad functional benefits in real-world aging models—effects that may be dismissed as “noise” but are likely the most translationally meaningful. In the case of CaAKG, substantial reductions in frailty occurred even when lifespan gains were modest—highlighting the decoupling of healthspan from longevity. By embracing both intrinsic and manifest aging, geroscience can better target what matters most: improving healthspan for the many—not just lifespan for the few.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102857"},"PeriodicalIF":12.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779286","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

Age-dependent efficacy of Bifidobacterium strains on cognitive impairment and dementia: A systematic review and meta-analysis 双歧杆菌菌株对认知障碍和痴呆的年龄依赖性疗效：一项系统综述和荟萃分析

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-31 DOI: 10.1016/j.arr.2025.102850

Wenliang Yu , Yao Li , Zeyang Liu , Siqi Hua , Ziyi Tan , Wei Tang , Mengyue Gao , Xiaoran Zhou , Zichun Hua

{"title":"Age-dependent efficacy of Bifidobacterium strains on cognitive impairment and dementia: A systematic review and meta-analysis","authors":"Wenliang Yu , Yao Li , Zeyang Liu , Siqi Hua , Ziyi Tan , Wei Tang , Mengyue Gao , Xiaoran Zhou , Zichun Hua","doi":"10.1016/j.arr.2025.102850","DOIUrl":"10.1016/j.arr.2025.102850","url":null,"abstract":"<div><h3>Objective</h3><div>Cognitive impairment and dementia are prevalent and costly diseases, affecting 5–8 % of individuals aged 60 and above globally. <em>Bifidobacterium</em>, a low-cost probiotic, has shown potential in treating dementia, but its efficacy remains controversial. To investigate the effects of <em>Bifidobacterium</em> on various dementia-related functional tests and biomarkers in different patient populations with cognitive impairment and dementia.</div></div><div><h3>Methods</h3><div>Systematic searches were conducted on February 15, 2025, across Embase, PubMed, Medline, Wanfang, and ClinicalTrials.gov. The risk of bias was assessed using NOS. The study is registered with PROSPERO (CRD42023460809).</div></div><div><h3>Results</h3><div>After rigorous screening, 18 studies encompassing 1195 patients were included. The results revealed that <em>Bifidobacterium</em> significantly improved cognitive function (MMSE, WMD = 2.26, 95 % CI = 1.69–2.83, compared to placebo: p = 0.049), particularly in patients under 70 (MMSE, WMD = 2.81, 95 % CI = 1.97–3.65). For patients over 70, better outcomes were achieved without <em>B. breve</em>-based treatments (MMSE, WMD = 2.43, 95 % CI = 1.76–3.09, compared to the group age under 70 or the group over 70 and receiving <em>B. breve</em>-based treatments: p = 0.0133). Additionally, <em>Bifidobacterium</em> significantly enhance patients’ memory, language, visuospatial, attention and executive abilities, potentially through the downregulation of triglycerides (WMD = −19.52, 95 % CI = −32.28 to −6.66, p = 0.039) and MDA (SMD = −0.72, 95 % CI = −1.07 to −0.37, p = 0.0057).</div></div><div><h3>Conclusions</h3><div>These findings provide key insights into the efficacy of <em>Bifidobacterium</em>, supporting personalized treatment strategies and reducing the treatment burden for patients with cognitive impairment and dementia.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102850"},"PeriodicalIF":12.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763946","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

Exercise as elixir to combat cardiovascular ageing 运动是对抗心血管老化的灵丹妙药。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-29 DOI: 10.1016/j.arr.2025.102848

Zihang Feng , Yuan Xing , Wei Yi , Feng Gao , Yang Sun , Xing Zhang

{"title":"Exercise as elixir to combat cardiovascular ageing","authors":"Zihang Feng , Yuan Xing , Wei Yi , Feng Gao , Yang Sun , Xing Zhang","doi":"10.1016/j.arr.2025.102848","DOIUrl":"10.1016/j.arr.2025.102848","url":null,"abstract":"<div><div>The global demographic shift towards an ageing population has rendered cardiovascular ageing and its associated pathologies a growing challenge for health. Emerging evidence highlights the critical role of exercise in mitigating age-associated cardiovascular alterations in structure and function and preventing ageing-associated cardiovascular diseases. However, the precise molecular mechanisms mediating these exercise-induced benefits in promoting healthy cardiovascular ageing remains incompletely mapped. Current progresses suggest that exercise exerts its anti-ageing effects through multiple synergistic mechanisms, including attenuation of conventional cardiovascular risk factors, cardiovascular structural remodeling, metabolic optimization, mitochondrial functional enhancement, and exerkine-mediated inter-tissue communication. These mechanisms collectively contribute to a more healthy cardiovascular ageing. Gaining a deeper insight into how exercise promotes healthy cardiovascular ageing not only advances our understanding of cardiovascular ageing but also illuminates potential approaches to prevent cardiovascular ageing and treat cardiovascular diseases. This review systematically discusses contemporary findings on exercise-mediated anti-cardiovascular ageing, and critically evaluates potential clinical applications and future research directions in the field.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102848"},"PeriodicalIF":12.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762639","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

Histopathological and ultrastructural changes in different cell types during ischemic and hemorrhagic stroke 缺血性和出血性脑卒中不同细胞类型的组织病理学和超微结构变化。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-25 DOI: 10.1016/j.arr.2025.102846

Houlian Zhang , Na Xing , Junmin Wang , Jing Zhang , Cao Jia , Yifei Li , Hualin Fan , Yiying Liu , Fatemeh Dialameh , Nannan Cheng , Yanyan Sun , Junyang Wang , Menglu Wang , Moxin Wu , Xiaoping Yin , Wei Zhu , Jing Li , Jiewen Zhang , Chao Jiang , Fei Xing , Jian Wang

{"title":"Histopathological and ultrastructural changes in different cell types during ischemic and hemorrhagic stroke","authors":"Houlian Zhang , Na Xing , Junmin Wang , Jing Zhang , Cao Jia , Yifei Li , Hualin Fan , Yiying Liu , Fatemeh Dialameh , Nannan Cheng , Yanyan Sun , Junyang Wang , Menglu Wang , Moxin Wu , Xiaoping Yin , Wei Zhu , Jing Li , Jiewen Zhang , Chao Jiang , Fei Xing , Jian Wang","doi":"10.1016/j.arr.2025.102846","DOIUrl":"10.1016/j.arr.2025.102846","url":null,"abstract":"<div><div>Stroke is a disease of the central nervous system that leads to high rates of morbidity and mortality, along with limited treatment options. This condition is frequently linked to pathologic alterations at the ultrastructural level within diverse neuronal components, including cell bodies, neurites, and synapses, as well as in glial cells like astrocytes, microglia, and oligodendrocytes. These changes include alterations in the shape and size of cell bodies, disruption of neurites, and changes in the density and distribution of synapses. The blood-brain barrier, a crucial component of the brain's defense system, is also compromised following a stroke, leading to further complications. Although stroke research has significantly advanced, there is still a lack of comprehensive reviews on ultrastructural pathological changes. Given the current challenges in treating stroke, identifying dynamic subcellular structural changes can improve our understanding of the complex pathologic processes after a stroke, ultimately enhancing clinical diagnosis and therapeutic strategies. This review aims to summarize and analyze the ultrastructural changes documented through transmission electron microscopy in both ischemic and hemorrhagic stroke, providing insights for future research and developing novel treatments.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102846"},"PeriodicalIF":12.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735956","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

Sphk2 in ischemic stroke pathogenesis: Roles, mechanisms, and regulation strategies Sphk2在缺血性卒中发病机制中的作用、机制和调控策略

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-25 DOI: 10.1016/j.arr.2025.102844

Mengzhao Feng , Qi Qin , Kaiyuan Zhang , Fang Wang , Dengpan Song , Mengyuan Li , Yuan An , Zhihua Li , Fuyou Guo

{"title":"Sphk2 in ischemic stroke pathogenesis: Roles, mechanisms, and regulation strategies","authors":"Mengzhao Feng , Qi Qin , Kaiyuan Zhang , Fang Wang , Dengpan Song , Mengyuan Li , Yuan An , Zhihua Li , Fuyou Guo","doi":"10.1016/j.arr.2025.102844","DOIUrl":"10.1016/j.arr.2025.102844","url":null,"abstract":"<div><div>Ischemic stroke, a leading cause of mortality and long-term disability worldwide, is characterized by acute cerebral artery occlusion leading to neuronal death and functional deficits. Despite advances in reperfusion therapies, the lack of effective neuroprotective agents underscores the need for novel therapeutic strategies targeting secondary injury mechanisms. Sphingosine kinase 2 (Sphk2) has emerged as a pivotal regulator in ischemic stroke pathogenesis, mitigating blood-brain barrier leakage, neuroinflammation, and neuronal survival through its downstream metabolite, sphingosine-1-phosphate. This review comprehensively examines the roles and mechanisms of Sphk2 in ischemic stroke, highlighting its potential in anti-inflammation and neuroprotection. We discuss current therapeutic approaches targeting Sphk2, including pharmacological activation, natural compounds and gene therapy. Future directions focus on developing Sphk2-specific agonists, optimizing delivery strategies, and exploring cell type-specific adeno-associated virus vectors and engineered exosomes modulation to maximize therapeutic efficacy while minimizing off-target effects. By synthesizing current knowledge and identifying gaps, this review provides a roadmap for harnessing Sphk2 as a therapeutic target to improve stroke outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102844"},"PeriodicalIF":12.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723703","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

Gut-brain relationship in dementia and Alzheimer's disease: Impact on stress and immunity 痴呆和阿尔茨海默病的肠脑关系：对压力和免疫的影响。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-23 DOI: 10.1016/j.arr.2025.102843

Upasana Mukherjee , P. Hemachandra Reddy

{"title":"Gut-brain relationship in dementia and Alzheimer's disease: Impact on stress and immunity","authors":"Upasana Mukherjee , P. Hemachandra Reddy","doi":"10.1016/j.arr.2025.102843","DOIUrl":"10.1016/j.arr.2025.102843","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is increasingly recognized as a condition shaped not only by central nervous system pathology but also by complex, bidirectional interactions between the gut, brain, and immune system. This review synthesizes emerging evidence on gut-brain-immune dysregulation in AD, with particular attention to how chronic stress, microbial imbalance, and neuroimmune signaling converge to influence disease risk and progression. We move beyond traditional microbiome-focused perspectives to incorporate non-microbial gut-derived mediators, including enteroendocrine hormones, bile acids, and vagal neuropeptides, which contribute to immune modulation, neurotransmission, and brain homeostasis. Importantly, we highlight that AD-related neurodegeneration can also feedback to impair gastrointestinal function and microbial composition, creating a self-reinforcing pathological loop. The review integrates recent findings on the role of host genetic polymorphisms, such as APOE4 and TREM2, in modulating gut permeability, immune tone, and microbiota profiles—emphasizing a systems biology model in which genome-microbiome interactions shape AD susceptibility. We also explore how single-cell omics technologies and multi-organ frameworks are redefining our understanding of gut-brain-immune circuits at cellular resolution. The translational section critically evaluates current and potential therapeutic strategies, including dietary, microbial, behavioral, and endocrine interventions, while addressing the challenges of applying preclinical findings to diverse human populations across the disease spectrum. By incorporating age-, stage-, and genotype-specific considerations, this review offers a comprehensive and timely synthesis of the gut-brain-stress axis in AD, positioning it as a key frontier in mechanistic research and precision therapeutic development.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102843"},"PeriodicalIF":12.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719175","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

Mitochondrial dysfunction in postoperative cognitive dysfunction: From preclinical mechanisms to multimodal diagnostics and precision intervention 术后认知功能障碍中的线粒体功能障碍：从临床前机制到多模式诊断和精确干预。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-23 DOI: 10.1016/j.arr.2025.102845

Fengying Liu , Xiaodong Wu , Zilin Wang , Ao Li , Yuan Luo , Jiangbei Cao

{"title":"Mitochondrial dysfunction in postoperative cognitive dysfunction: From preclinical mechanisms to multimodal diagnostics and precision intervention","authors":"Fengying Liu , Xiaodong Wu , Zilin Wang , Ao Li , Yuan Luo , Jiangbei Cao","doi":"10.1016/j.arr.2025.102845","DOIUrl":"10.1016/j.arr.2025.102845","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) poses a significant clinical challenge with far-reaching implications for patient recovery and long-term quality of life. Growing evidence underscores the central role of mitochondrial dysfunction in the pathogenesis of POCD, uncovering an intricate interplay of molecular mechanisms that influence cognitive function. This study reviews the key mechanistic pathways involving mitochondria: bioenergetic impairment and metabolic irregularities, oxidative stress pathways and neuroinflammation, disruptions in calcium signaling, and deficiencies in mitochondrial quality control mechanisms-including kinetic abnormalities, defective mitophagy, and mitochondrial genetic material damage. Each of these pathways acts as a potential molecular nexus contributing to the cognitive decline in post-surgery, revealing the multifaceted nature of POCD progression. Furthermore, the review synthesizes recent advances in diagnostic and preventive strategies targeting mitochondrial dysfunction, bridging preclinical discoveries with clinical relevance. By delineating the role of mitochondria in the molecular landscape of POCD, this review not only clarifies the disease’s pathogenic foundations but also paves the way for future translational research in mitochondria-targeted diagnostics and interventions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102845"},"PeriodicalIF":12.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719197","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

Bidirectional regulation of neuronal autophagy in ischemic stroke: Mechanisms and therapeutic potential 缺血性脑卒中中神经元自噬的双向调节：机制和治疗潜力。

IF 12.4 1区医学

Ageing Research Reviews Pub Date : 2025-07-22 DOI: 10.1016/j.arr.2025.102842

Yige Wu , Zhu Li , Tao Ding, Yunqi Yang, Congmin Wei, Shanshan Zhang, Xiang Fan

{"title":"Bidirectional regulation of neuronal autophagy in ischemic stroke: Mechanisms and therapeutic potential","authors":"Yige Wu , Zhu Li , Tao Ding, Yunqi Yang, Congmin Wei, Shanshan Zhang, Xiang Fan","doi":"10.1016/j.arr.2025.102842","DOIUrl":"10.1016/j.arr.2025.102842","url":null,"abstract":"<div><div>Ischemic stroke, characterized by cerebral blood flow disruption, triggers complex pathophysiological responses where neuronal autophagy plays a bidirectional regulation role in neuroprotection and injury. Autophagy, activated by energy deprivation, hypoxia, and endoplasmic reticulum stress, dynamically regulates neuronal survival through selective autophagy (e.g., mitophagy, endoplasmic reticulum-phagy, ferritinophagy) of damaged organelles and protein aggregates. Early-stage moderate autophagy exerts neuroprotection by clearing cytotoxic aggregates and maintaining metabolic homeostasis, while excessive or prolonged autophagy exacerbates neuronal death via energy depletion and activation of apoptosis/ferroptosis pathways. Key regulatory mechanisms involve AMPK/mTOR, PI3K/AKT, HIF-1, and MAPK signaling, which modulate autophagic flux and crosstalk with oxidative stress, inflammation, and mitochondrial dynamics. Notably, selective autophagy pathways exhibit spatiotemporal specificity: mitophagy <em>via</em> PINK1/Parkin and BNIP3/FUNDC1 balances mitochondrial quality control, while ferritinophagy-mediated iron dysregulation drives ferroptosis. Pharmacological interventions targeting autophagy-related pathways (e.g., rapamycin, 3-MA, NCOA4 inhibitors) or natural compounds (e.g., Ginkgolide B, HSYA) demonstrate therapeutic potential by fine-tuning autophagic activity. However, challenges remain in defining optimal autophagy thresholds and translating preclinical findings to clinical applications. This review highlights the critical importance of spatiotemporal regulation of neuronal autophagy to develop precise neuroprotective strategies for ischemic stroke, with a particular focus on the interaction between autophagy modulators and the pathophysiological mechanisms of ischemia.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102842"},"PeriodicalIF":12.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710234","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 evolution of Alzheimer’s disease: From mitochondria to microglia 阿尔茨海默病的进化：从线粒体到小胶质细胞。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-07-21 DOI: 10.1016/j.arr.2025.102838

Feng-ge Yang , Yu-lin Liang , Xu Wang , Jun-ting Wang , Wei Gao , Qiu-yan Ye , Xue-yuan Li , Yu Yang , Hong-lin Li

{"title":"The evolution of Alzheimer’s disease: From mitochondria to microglia","authors":"Feng-ge Yang , Yu-lin Liang , Xu Wang , Jun-ting Wang , Wei Gao , Qiu-yan Ye , Xue-yuan Li , Yu Yang , Hong-lin Li","doi":"10.1016/j.arr.2025.102838","DOIUrl":"10.1016/j.arr.2025.102838","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) represents the most prevalent neurodegenerative disorder worldwide. Recent studies highlights that mitochondrial dysfunction drives alterations in microglial function, serving as a pivotal mechanism in the pathogenesis and progression of AD. Increasingly, there is evidence that mitochondrial dysfunction encompasses energy metabolism deficits, heightened oxidative stress, impaired mitochondrial dynamics, disrupted autophagy, and calcium homeostasis imbalances. These impairments modulate microglial activation states, precipitating exacerbated neuroinflammation, altered phagocytic capacity, and increased cellular apoptosis, collectively contributing to microglial dysfunction. This paper presents a narrative review on the relationship between mitochondrial dysfunction and AD, elucidating the impact of mitochondrial impairment on microglia. It summarizes therapeutic strategies that target mitochondria to modulate microglial function, aiming to prevent and treat AD. The goal is to provide new perspectives and insights for AD research and treatment, contributing to improving patients' quality of life and prognosis.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102838"},"PeriodicalIF":12.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700599","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