Ageing Research Reviews最新文献

{"title":"CRISPR/cas genome editing for neurodegenerative diseases: Mechanisms, therapeutic advances, and clinical prospects","authors":"Kalpana Pandya ,&nbsp;Devendra Kumar","doi":"10.1016/j.arr.2025.102922","DOIUrl":"10.1016/j.arr.2025.102922","url":null,"abstract":"<div><div>Neurodegenerative diseases such as Alzheimerʼs disease (AD), Parkinsonʼs disease (PD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebral Ataxia (SCA), and Huntingtonʼs disease (HD) are major global health challenges. Current treatments are only symptomatic and do not address the underlying pathogenic genetic mechanisms. The development of the CRISPR/Cas genome editing technologies, has increased possibilities for targeted repair of pathological mutations. CRISPR/Cas9, Cas12, and Cas13 systems enable targeted editing and transcriptome modulation in various preclinical models. CRISPR/Cas9 disruption of mutant APP, Tau, and LRRK2 genes, reducing toxic protein aggregration in AD models has restored normal genetic function. While correction of CAG nucleotide repeats in HD, and reduction of alpha-synuclein expression in PD. RNA targeting systems like Cas13 offers additional therapeutics potential by selectively degrading disease assciated transcript without altering genomic DNA. Advancements in engineered Cas variants with enhanced specificity, such as SpCas9-HF1, base editors and prime editors, with innovative delivery strategies including adeno-associated virus (AAVs) and nanoparticle-based systems, have improved genome editing. However, challenges remain, including off-target effects, mosaicism, and delivery across the BBB, and long-term safety. Ethical consideration focuses on somatic versus germline editing, equitable access, and regulatory oversight. While somatic editing shows acceptance in treating neurological disorders. Germline interventions face strict regulations due to potential multigeneration impacts. Collectively, these technologies are the vanguard of precision molecular medicine, advancing from symptom management towards potentially curative gene therapies for neurological disorders.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102922"},"PeriodicalIF":12.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318922","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}

{"title":"Targeting mitochondrial microRNAs in cardiovascular pathologies: A new frontier in precision cardiology","authors":"Satinder Kaur ,&nbsp;Gurjit Kaur Bhatti ,&nbsp;Naina Khullar ,&nbsp;Jasvinder Singh Bhatti","doi":"10.1016/j.arr.2025.102920","DOIUrl":"10.1016/j.arr.2025.102920","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) continue to rise at an alarming rate, contributing to millions of deaths globally. Among them, myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of mortality. Despite extensive research, MI remains incurable, and its complete eradication has yet to be achieved. Mitochondria play a central role in the pathogenesis and potential treatment of MI, and recent studies have identified mitochondrial microRNAs (mito-miRs) as promising molecular regulators. Although the precise mechanisms of mito-miRs remain incompletely understood, emerging evidence suggests their involvement in regulating mitochondrial metabolism, dynamics, ROS production, bioenergetics, and mitochondrial biogenesis. Additionally, mito-miRs influence several forms of programmed cell death, including apoptosis, necrosis, ferroptosis, and pyroptosis. The exact processes governing the translocation of these miRNAs into mitochondria and their intracellular actions remain elusive. Notably, specific miRNAs have been shown to target key cardiac cell types, including cardiomyocytes, endothelial cells, and fibroblasts. Deciphering their mechanistic roles could enable the development of targeted mito-miRNA-based therapeutics. Moreover, their therapeutic efficacy may be enhanced by integrating mito-miRs with stem cell therapies and bioactive compounds, particularly when delivered via nanoparticle-based formulations to ensure targeted delivery within the cardiac microenvironment.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102920"},"PeriodicalIF":12.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318930","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}

{"title":"A receptor for glycation end products (RAGE) is a key transmitter between garb-aging and inflammaging","authors":"Zulfiya G. Guvatova ,&nbsp;Anna Vakhrusheva ,&nbsp;Alexey Moskalev","doi":"10.1016/j.arr.2025.102919","DOIUrl":"10.1016/j.arr.2025.102919","url":null,"abstract":"<div><div>A receptor for glycation end products (RAGE) plays a key role in the pathogenesis of many chronic diseases associated with aging. Acting as a multi-ligand sensor, RAGE is able to bind a wide range of stimuli, which fuels inflammation. This makes it a key link between garb-aging and inflammaging. We propose that RAGE functions as the missing molecular link between garb-aging, the progressive buildup of biological waste, and inflammaging, the chronic inflammatory state that drives degenerative disorders. This review summarizes current knowledge on RAGE structure, ligands, and signaling, highlighting its involvement in diabetes, cardiovascular, neurodegenerative, and inflammatory diseases, as well as therapeutic strategies targeting RAGE. By nominating RAGE as a central receptor of garb-aging, we outline new perspectives for combating age-associated pathologies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102919"},"PeriodicalIF":12.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310306","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}

{"title":"First unified time-course of Alzheimer’s-like pathology in the intracerebroventricular streptozotocin-rat model: A systematic review","authors":"Karen León-Arcia ,&nbsp;Jesús Andrade-Guerrero ,&nbsp;Humberto Martínez-Orozco ,&nbsp;Marcos M. Villegas-Rojas ,&nbsp;Isaac Pérez-Segura ,&nbsp;Isaac López Ramírez ,&nbsp;Alonso Vilches-Flores ,&nbsp;Magdalena Guerra-Crespo ,&nbsp;Sofía Y. Díaz-Miranda ,&nbsp;Luis O. Soto-Rojas","doi":"10.1016/j.arr.2025.102918","DOIUrl":"10.1016/j.arr.2025.102918","url":null,"abstract":"<div><div>This systematic review investigates the timeline of Alzheimer’s disease (AD)-like changes in the intracerebroventricular streptozotocin (ICV-STZ) rat model, a key tool for studying sporadic, non-genetic forms of AD. Following PRISMA guidelines, we analyzed 402 studies to characterize the progression of key pathological features, including cognitive deficits, insulin resistance, neurodegeneration, neuroinflammation, oxidative stress, tau pathology, amyloid aggregation, blood-brain barrier (BBB) dysfunction, and alterations in the gut-brain axis. Most studies used young male Wistar rats, revealing a sex and age bias. Results show cognitive impairment beginning within the first 24 h after ICV-STZ administration and persisting beyond 121 days, accompanied by early molecular changes, including disrupted insulin signaling, apoptosis (on day 1), and oxidative stress (on day 7). These events triggered a cascade of neuroinflammation, synaptic loss, tau hyperphosphorylation, amyloid plaque formation/accumulation, and neuronal death that closely resemble human AD. This work provides the first unified time-course of these alterations, confirming the model’s ability to mimic the complexity of AD, while also identifying important gaps, such as its limited use of female and aged rats, underexplored areas like the BBB and gut-brain axis, and specific brain regions that require further investigation. The sporadic AD rat model induced by ICV-STZ serves as a powerful and versatile platform for dissecting the multifactorial nature of AD, identifying early biomarkers, and accelerating the development of targeted and disease-modifying therapies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102918"},"PeriodicalIF":12.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304914","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}

{"title":"The interactome era: Integrating RNA-seq, proteomics, and network biology to decode cellular senescence","authors":"Mohd Shahzaib ,&nbsp;Domenico Aprile ,&nbsp;Tiziana Squillaro ,&nbsp;Nicola Alessio ,&nbsp;Gianfranco Peluso ,&nbsp;Giovanni Di Bernardo ,&nbsp;Umberto Galderisi","doi":"10.1016/j.arr.2025.102916","DOIUrl":"10.1016/j.arr.2025.102916","url":null,"abstract":"<div><div>Cellular senescence is a dynamic state in which cells permanently withdraw from the cell cycle while continuing to reshape their internal and external environment. It is characterized by persistent DNA damage responses, chromatin reorganization, and the secretion of a complex mixture of cytokines and proteases collectively known as the senescence-associated secretory phenotype (SASP). Transcriptomic and proteomic studies have defined key markers, including CDKN2A, CDKN1A, TP53, and SASP factors, but these approaches provide only static inventories. They do not explain how regulatory programs are executed through protein interactions that assemble, dissolve, and reorganize over time. Interactomics now fills this gap. Advances such as affinity purification mass spectrometry (AP-MS), proximity labeling (BioID/TurboID), and cross-linking mass spectrometry (XL-MS) reveal that senescence is driven not by single molecules but by the rewiring of protein–protein interactions (PPIs). These dynamic networks stabilize DNA damage response hubs, restructure chromatin and the nuclear lamina, regulate SASP secretion, and remodel metabolism. By integrating interactomic data with transcriptomic and proteomic profiles, it is now possible to uncover therapeutic vulnerabilities and guide the design of senolytics, senomorphics, and strategies that block senescence escape. Important challenges remain. Weak or transient interactions are often lost, background signals can obscure specificity, and membrane complexes are under-represented. Emerging single-cell and spatial technologies are beginning to overcome these limitations, revealing how senescence differs across tissues, contexts, and disease states. In essence, senescence is not just a change in gene expression but a reorganization of the cell’s communication networks. Interactomics offers the framework needed to decode this complexity and to design precision therapies for aging and age-related disease.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102916"},"PeriodicalIF":12.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287996","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}

{"title":"Extracellular vesicle-based biosensors for Alzheimer’s disease: A new frontier in precision diagnostics","authors":"Jinjin Pei ,&nbsp;Nishanthi Chella Perumal ,&nbsp;Panpan Meng ,&nbsp;Qianfa Long ,&nbsp;Chella Perumal Palanisamy","doi":"10.1016/j.arr.2025.102904","DOIUrl":"10.1016/j.arr.2025.102904","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, remains a diagnostic challenge due to its asymptomatic early stages and the lack of reliable, non-invasive biomarkers. Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane-bound particles released by cells into biological fluids and have emerged as promising carriers of disease-specific biomarkers. These vesicles reflect the physiological and pathological state of their parental cells, encapsulating proteins, lipids, and nucleic acids relevant to AD pathology, such as amyloid-β, tau, and microRNAs. Recent advances in biosensor technology have enabled the development of highly sensitive and specific platforms to detect EV-associated biomarkers. Integrating EVs with biosensing approaches—ranging from electrochemical and optical sensors to nanomaterial-based systems—represents a promising strategy for early AD diagnosis, monitoring disease progression, and evaluating therapeutic efficacy. However, these technologies remain largely in preclinical or early translational stages, with further validation required in large-scale clinical cohorts. This review provides a comprehensive overview of the recent progress in EV-based biosensor technologies, highlighting their analytical performance, detection principles, and clinical relevance in AD diagnostics. Furthermore, we discuss the current challenges, such as standardization in EV isolation and characterization, and propose future perspectives for translating these innovative diagnostic tools into clinical practice. The integration of EV biology with advanced biosensing technologies represents an emerging advancement with strong potential for precision medicine in AD, although clinical translation will require rigorous validation and standardization.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102904"},"PeriodicalIF":12.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236097","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}

{"title":"Prevalence of frailty in cardiac transthyretin amyloidosis: A systematic review and meta-analysis","authors":"Alberto Finazzi ,&nbsp;Emma Esposito ,&nbsp;Chiara Riva ,&nbsp;Elisabetta Mangili ,&nbsp;Lorenzo Lodovici ,&nbsp;Adriana Antonella Bruni ,&nbsp;Elena Pinardi ,&nbsp;Maria Cristina Ferrara ,&nbsp;Daniela Pini ,&nbsp;Antonella Zambon ,&nbsp;Francesco Musca ,&nbsp;Stefano Perlini ,&nbsp;Chukwuma Okoye ,&nbsp;Giuseppe Bellelli","doi":"10.1016/j.arr.2025.102903","DOIUrl":"10.1016/j.arr.2025.102903","url":null,"abstract":"<div><h3>Background</h3><div>Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Frailty is common among older adults and strongly associated with adverse outcomes. However, its prevalence and clinical relevance in the context of CA have not been systematically examined. This review aimed to assess the prevalence of frailty in CA and qualitatively synthesize the evidence on its association with clinical outcomes.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis of observational studies was conducted to assess frailty prevalence in CA. Databases searched included Embase, PubMed, CINAHL, Cochrane Library, and Google Scholar up to April 15, 2025. Studies reporting frailty prevalence in CA patients were included. Six assessors independently screened the articles, extracted data, and resolved conflicts by consensus. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale.</div></div><div><h3>Results</h3><div>Out of 565 articles identified, six studies met inclusion criteria, including a total of 1422 participants with cardiac transthyretin amyloidosis (ATTR-CA). Reported frailty prevalence ranged from 14.5 % to 75 %, depending on the assessment method. A meta-analysis restricted to studies using the Clinical Frailty Scale (N = 1164) yielded a pooled frailty prevalence of 66 % (95 % CI, 57–74 %), with substantial heterogeneity (I² = 89.1 %). Frailty was consistently associated with higher mortality and poorer quality of life.</div></div><div><h3>Conclusions</h3><div>Frailty is highly prevalent in individuals with ATTR-CA and is independently associated with adverse clinical outcomes. These findings support the routine evaluation of frailty in the management of individuals with CA. PROSPERO registration (CRD42024607807).</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102903"},"PeriodicalIF":12.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236092","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}

{"title":"Sirtuins in Parkinson's disease: Molecular mechanisms and pathophysiological roles","authors":"Xiang Li ,&nbsp;Xuequn Luo ,&nbsp;Xueqin Cao ,&nbsp;Elizabeth Rosalind Thomas ,&nbsp;Wenjun Wang ,&nbsp;Xiaogang Zhou ,&nbsp;Shiying Zhou ,&nbsp;Anguo Wu ,&nbsp;Ruixia Gao ,&nbsp;Kezhi Liu ,&nbsp;Jianming Wu","doi":"10.1016/j.arr.2025.102902","DOIUrl":"10.1016/j.arr.2025.102902","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a progressive neurodegenerative disorder that is associated with mitochondrial dysfunction, oxidative stress, neuroinflammation, and abnormal protein aggregation. The silent information regulator 2 (Sir2) family of proteins, known as sirtuins (SIRT1 - SIRT7), is nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylases that regulate important signal transduction pathways in both prokaryotes and eukaryotes. An increasing number of studies revealed that sirtuins play diverse roles in cellular homeostasis, such as metabolic regulation, oxidative stress response, apoptosis, organelle protection, and gene stability. Intriguingly, growing evidence suggests that sirtuins may serve as pivotal molecular mediators in PD, yet a comprehensive synthesis of their roles in this disorder is lacking. Although the precise pathogenesis of PD remains unmapped, identifying common molecular nodes could offer effective therapeutic strategies. In this review, we present the first systematic integration of current knowledge on the distinct contributions of individual sirtuins to PD pathophysiology offering promising molecular targets for the treatment of PD. Unlike previous studies focusing on isolated aspects of sirtuin biology, our work uniquely consolidates the multifaceted mechanisms by which sirtuins modulate PD, offering a holistic perspective on their therapeutic potential. We underscore the transformative potential of sirtuin modulation, positioning a promising and unexplored frontier in neurodegenerative disease therapy. This work aims to provide new insights into potential sirtuin-targeted therapy of PD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102902"},"PeriodicalIF":12.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187825","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}

{"title":"Biomarkers of female reproductive aging in gerotherapeutic clinical trials","authors":"Paula Benny ,&nbsp;Ajla Hodzic Kuerec ,&nbsp;Jessica Yu ,&nbsp;Jovin Lee ,&nbsp;Qian Yang ,&nbsp;Andrea Britta Maier ,&nbsp;Zhongwei Huang","doi":"10.1016/j.arr.2025.102901","DOIUrl":"10.1016/j.arr.2025.102901","url":null,"abstract":"<div><div>The United Nations World Population Statistics reported that 10 % of the global population, approximately 830 million people, were aged 65 years and older in 2024. This number is projected to double, reaching almost 20 % or 1.7 billion, by 2050. With a growing aging population world-wide, age-associated diseases are also expected to increase, which has prompted research into geroscience to optimize the healthspan of aging individuals. For women, menopause significantly increases the risks of ageassociated diseases, which highlights the importance of sex-specific approaches to precision geromedicine. At present, there is a limited understanding of biomarkers of female reproductive aging and its inclusion into gerotherapeutic clinical trials. Previous gerotherapeutic trials have not specifically evaluated reproductive aging, instead focusing primarily on cardiometabolic, neurocognitive, and musculoskeletal outcomes. In contrast, clinical studies targeting subfertility often assess biomarkers such as AMH, FSH, and LH, while trials addressing menopausal symptoms commonly apply the STRAW+ 10 criteria for reproductive staging. Only recently has ovarian aging been recognized as a critical determinant of women’s overall health, extending beyond its role in fertility. Therefore, this article discusses the available (FSH, AMH, Inhibin, antral follicle count) as well as the emerging biomarkers (estradiol, progesterone, LH, Sirtuin- 1, microRNAs, menstrual blood markers, epigenetic markers, ovarian stiffness, vaginal microbiome markers, survey information) of female reproductive aging and a protocol for evaluating the impact of gerotherapeutics in clinical trials. Using an example of a Phase 2 Clinical Trial (1 year), short-term (every 3 months) and long-term (every 6 months) follow-ups can be performed. Importantly, female reproductive lifestage should be taken into consideration when prescribing gerotherapeutics to improve female reproductive aging, ultimately optimizing the health and healthspan of females.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102901"},"PeriodicalIF":12.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152287","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}

{"title":"Glymphatic system and intracerebral hemorrhage: Identifying molecular targets for future therapeutic advancements","authors":"Ushmita Mukherjee ,&nbsp;Sanjana Chowdhury ,&nbsp;Kishan Kumar Nagada ,&nbsp;MD Mujtahid Hasan ,&nbsp;Bijoyani Ghosh ,&nbsp;Avdhoot Joshi ,&nbsp;Aishika Datta ,&nbsp;Jayanta Roy ,&nbsp;Pallab Bhattacharya","doi":"10.1016/j.arr.2025.102900","DOIUrl":"10.1016/j.arr.2025.102900","url":null,"abstract":"<div><div>The glymphatic system is an essential component in modulating brain health and clearing out toxins from the central nervous system (CNS). The glymphatic system, especially the perivascular space, undergoes significant alterations during CNS inflammation. Various cerebrovascular disorders have implicated glymphatic dysfunction as the major contributing factor for cerebral edema, neuroinflammation, as well as damage to the blood-brain barrier (BBB). Intracerebral hemorrhage (ICH) is a major life-threatening stroke subtype with limited therapies available. ICH results from the rupture of cerebral arteries, accumulation of the blood and hematoma formation in the brain parenchyma. The toxic degradation components from the hematoma further exacerbates the oxidative stress, inflammatory response and cerebral edema, worsening the BBB disruption as well as the neurological outcomes post-ICH. Thus, making it imperative to understand the underlying mechanisms of secondary brain injury (SBI) and create targeted therapeutic strategies to improve patient recovery. Owing to the involvement of the glymphatic system in clearing out debris, it may contribute in alleviating SBI following ICH. In this review we intend to gain a better understanding of the glymphatic system’s role in mitigating SBI as well as potential therapeutic approaches that target this system to improve patient recovery and reduce damage post-ICH.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102900"},"PeriodicalIF":12.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152304","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}