Ageing Research Reviews最新文献

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Nuclear mitochondrial DNA transfer revisited: From genomic noise to hallmark of aging 重新审视核线粒体DNA转移:从基因组噪音到衰老的标志
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-04 DOI: 10.1016/j.arr.2025.102892
Emanuele Marzetti , Rosa Di Lorenzo , Riccardo Calvani , Helio José Coelho-Junior , Vito Pesce , Francesco Landi , Christiaan Leeuwenburgh , Anna Picca
{"title":"Nuclear mitochondrial DNA transfer revisited: From genomic noise to hallmark of aging","authors":"Emanuele Marzetti ,&nbsp;Rosa Di Lorenzo ,&nbsp;Riccardo Calvani ,&nbsp;Helio José Coelho-Junior ,&nbsp;Vito Pesce ,&nbsp;Francesco Landi ,&nbsp;Christiaan Leeuwenburgh ,&nbsp;Anna Picca","doi":"10.1016/j.arr.2025.102892","DOIUrl":"10.1016/j.arr.2025.102892","url":null,"abstract":"<div><div>Nuclear insertions of mitochondrial DNA (mtDNA) segments (NUMTs) represent an evolutionarily conserved phenomenon originating from the ancient endosymbiotic relationship between mitochondria and host cells. These insertions predominantly localize near intergenic or regulatory regions and are often enriched in tissues with high metabolic activity. Once regarded as inert pseudogenes or genomic artifacts, NUMTs are now recognized as dynamic elements capable of modulating nuclear architecture and cellular function. Advances in whole-genome sequencing have revealed a remarkable diversity of NUMTs across species, including polymorphic variants in humans that suggest ongoing NUMTogenesis. Stress-induced mitochondrial damage promotes mtDNA release and subsequent nuclear integration via non-homologous end joining, a mechanism that may be exacerbated in aging tissues. Studies suggest that NUMTs may intersect with some biological hallmarks of aging. Recently, NUMT accumulation in the brain was shown to correlate with cognitive decline and reduced lifespan, implicating NUMTs in biological aging and associated conditions. Additionally, NUMTs have been observed in oncogenic loci, suggesting potential roles in carcinogenesis. This review synthesizes current evidence on the molecular mechanisms underpinning NUMT generation and explores their intersection with aging biology. We examine how NUMTs may influence mitochondrial−nuclear communication, promote inflammation, and affect telomere dynamics and cellular senescence. We also highlight the relevance of understanding the biological impact of NUMTs across life stages and disease states to inform novel biomarkers and therapeutic strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102892"},"PeriodicalIF":12.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003610","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
TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration TNF在肥胖驱动的神经炎症和神经变性中作为代谢性炎症和体脑相互作用的中介
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-03 DOI: 10.1016/j.arr.2025.102891
Chih Hung Lo , Jialiu Zeng
{"title":"TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration","authors":"Chih Hung Lo ,&nbsp;Jialiu Zeng","doi":"10.1016/j.arr.2025.102891","DOIUrl":"10.1016/j.arr.2025.102891","url":null,"abstract":"<div><div>Body–brain interaction (BBI) plays a critical role in coordinating the communication between peripheral organs and the brain, contributing to the comorbidity of metabolic disorders and neurological disorders. In the context of obesity, one of the key mediators driving systemic and neuroinflammatory responses is the soluble form of tumor necrosis factor (TNF), which primarily signals through TNF receptor 1 (TNFR1) to regulate inflammation and cell death. In this review, we examine how TNF/TNFR1-mediated metabolic inflammation in obesity disrupts cellular homeostasis across multiple organ systems, including the brain. In peripheral tissues, TNF is overproduced and secreted by activated macrophages, leading to lipid dysmetabolism, insulin resistance, and metabolic dysfunction in key cell types such as adipocytes and hepatocytes. Elevated circulating TNF also increases the permeability of the blood–brain barrier, enabling peripheral inflammatory mediators to infiltrate the brain and activate glial cells, thereby amplifying neuroinflammation. Within the brain, TNF induces metabolic and autolysosomal dysfunction in neurons, resulting in elevated reactive oxygen species, accumulation of toxic protein aggregates, and impaired insulin signaling, contributing collectively to neuronal death and the progression of neurodegeneration. We further highlight the metabolic-inflammatory crosstalk within the BBI as a potential therapeutic target, focusing on anti-inflammatory strategies that modulate TNF/TNFR1 signaling. Lastly, we provide future perspectives on the implications of body–brain axes, cell type–specific mechanisms, and disease comorbidities in the context of obesity.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102891"},"PeriodicalIF":12.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003789","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
Ca2+/Calmodulin-dependent protein kinase II (CaMKII)-targeted drug discovery: Challenges and strategies Ca2+/钙调素依赖性蛋白激酶II (CaMKII)靶向药物发现:挑战和策略。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-03 DOI: 10.1016/j.arr.2025.102886
Xinmiao Tian , Xianghui Wang , Sichong Chen , Xuefei Sun , Dongxue Shao , Kuo Zhang , Qinghua Gao , Liying Hao
{"title":"Ca2+/Calmodulin-dependent protein kinase II (CaMKII)-targeted drug discovery: Challenges and strategies","authors":"Xinmiao Tian ,&nbsp;Xianghui Wang ,&nbsp;Sichong Chen ,&nbsp;Xuefei Sun ,&nbsp;Dongxue Shao ,&nbsp;Kuo Zhang ,&nbsp;Qinghua Gao ,&nbsp;Liying Hao","doi":"10.1016/j.arr.2025.102886","DOIUrl":"10.1016/j.arr.2025.102886","url":null,"abstract":"<div><div>Calcium (Ca<sup>2+</sup>)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is an emerging drug target for age-related diseases. It is a multifunctional kinase with complex activation modes, numerous isoforms, broad tissue distribution, and a dual role in health and disease. In particular, its isoforms share a high degree of conservation within the catalytic and regulatory domains, with only minor differences confined to the linker region. These characteristics of CaMKII make the development of selectively targeted inhibitors particularly challenging. Current CaMKII inhibitors can be classified into the following categories: CaM-binding site blockers (KN62, KN93); ATP-competitive inhibitors (AS105, GS-680, RA306, RA608, SMP-114, NP202, hesperadin); substrate-binding site blockers (AIP, AC3-I, CN21); and pathway-targeted novel modulators (e.g., Athycaltide-1). However, no CaMKII inhibitor has yet reached clinical approval. Nevertheless, CaMKII remains a compelling target due to its pivotal role in age-related pathologies. Several innovative approaches hold promise for overcoming current limitations, including: activating endogenous degradation of CaMKII by proteolysis-targeting chimeras (PROTACs), applying novel materials such as peptide- or nucleic acid-based agents and CRISPR-Cas9-mediated gene editing approaches, employing tissue-specific delivery systems and engineered drug molecules, and targeting disease-specific signaling pathways. Together, these strategies may pave the way for more precise and effective CaMKII-targeted interventions in aging-associated diseases.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102886"},"PeriodicalIF":12.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006975","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
Deep aging clocks: AI-powered strategies for biological age estimation 深度老化时钟:人工智能驱动的生物年龄估计策略
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-02 DOI: 10.1016/j.arr.2025.102889
Luma Srour , Yosra Bejaoui , James She , Tanvir Alam , Nady El Hajj
{"title":"Deep aging clocks: AI-powered strategies for biological age estimation","authors":"Luma Srour ,&nbsp;Yosra Bejaoui ,&nbsp;James She ,&nbsp;Tanvir Alam ,&nbsp;Nady El Hajj","doi":"10.1016/j.arr.2025.102889","DOIUrl":"10.1016/j.arr.2025.102889","url":null,"abstract":"<div><div>Several strategies have emerged lately in response to the rapid increase in the aging population to enhance health and life span and manage aging challenges. Developing such strategies is imperative and requires an assessment of biological aging. Several aging clocks have recently been developed to measure biological aging and to assess the efficacy of longevity interventions. Biological age better reflects a person’s actual age and is closely associated with health outcomes and time to mortality. Traditionally, most aging clocks assume that biological changes occur linearly over time. However, age-related changes do not necessarily follow a linear trajectory. Thus, “Deep Aging Clocks” have been developed to overcome previous clocks' limitations and better capture subtle changes that occur during aging. Here, we summarize the current deep aging clocks, including epigenetics, transcriptomics, metabolomics, microbiome, and imaging based clocks for age prediction. Recent advances in artificial intelligence (AI), utilizing deep learning techniques, have significantly enhanced the prediction of biological aging, and this would help improve aging clocks and accelerate efforts to reach longer and healthier lives.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102889"},"PeriodicalIF":12.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988401","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
Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases PPAR-γ共激活因子-1α的调控及其在线粒体功能和神经退行性疾病中的意义
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-02 DOI: 10.1016/j.arr.2025.102887
Ashwini Prem Kumar , Devaraj Thittayil Puthussery
{"title":"Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases","authors":"Ashwini Prem Kumar ,&nbsp;Devaraj Thittayil Puthussery","doi":"10.1016/j.arr.2025.102887","DOIUrl":"10.1016/j.arr.2025.102887","url":null,"abstract":"<div><div>Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, interacts with numerous transcription factors implicated in a wide spectrum of biological responses. It has been identified as a key player in the transcriptional regulation of many mitochondrial components. The activity of PGC1-α is regulated at multiple levels, such as gene expression, transcriptional, post-transcriptional, and post-translational modification. The purpose of this review is to highlight the data supporting PGC1-α-mediated regulation by transcriptional and post-translational modification. We summarize the mechanisms involved in PGC1-α regulation by phosphorylation (AMPK, p38 MAPK, Akt, and GSK3β), acetylation (GCN5, p300, and SRCC), and ubiquitination (E3-ubiquitin ligase). Moreover, the review focuses on the multidomain structure of PGC1-α, its expression in the brain, and the importance of PGC1-α-mediated mitochondrial functions.</div><div>Mitochondrial dysfunction and impaired energy metabolism are key characteristics of neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and multiple sclerosis. It is associated with reduced PGC1-α expression or activity, resulting in an imbalance in the maintenance of mitochondrial dynamics. In this backdrop, we additionally provide a comprehensive overview of the implication of PGC1-α in the pathogenesis of neurodegenerative disease. Overall, PGC1-α acts as a potential target for therapies to reduce mitochondrial dysfunction associated with neurodegenerative diseases and aid in neuroprotection.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102887"},"PeriodicalIF":12.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988400","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
Effectiveness of various exercise on neuropsychiatric symptoms among older adults with mild cognitive impairment or dementia: A systematic review and network meta-analysis 各种运动对轻度认知障碍或痴呆老年人神经精神症状的有效性:系统回顾和网络荟萃分析
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-01 DOI: 10.1016/j.arr.2025.102890
Qinghuan Kong , Kexin Huang , Shuang Li , Xinyun Li , Rui Han , Haiqi Yang , Yuhang Pu , Li Chen , Yong Jia
{"title":"Effectiveness of various exercise on neuropsychiatric symptoms among older adults with mild cognitive impairment or dementia: A systematic review and network meta-analysis","authors":"Qinghuan Kong ,&nbsp;Kexin Huang ,&nbsp;Shuang Li ,&nbsp;Xinyun Li ,&nbsp;Rui Han ,&nbsp;Haiqi Yang ,&nbsp;Yuhang Pu ,&nbsp;Li Chen ,&nbsp;Yong Jia","doi":"10.1016/j.arr.2025.102890","DOIUrl":"10.1016/j.arr.2025.102890","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the comparative efficacy of exercise for reducing neuropsychiatric symptoms (NPS) among older adults with mild cognitive impairment (MCI) or dementia.</div></div><div><h3>Methods</h3><div>Ten databases were systematically searched from their inception to April 29, 2025, with the latest update in July 13, 2025. Randomized controlled trials (RCTs) and quasi-experimental studies evaluating the effectiveness of exercise on NPS in older adults with MCI or dementia were included. Risk of bias was assessed using the Risk of Bias tool (RoB 2) tool for RCTs and the Joanna Briggs Institute (JBI) critical appraisal checklists. A random-effects network meta-analysis model was employed to synthesize all available evidence. The registration number of this study is CRD420251087869.</div></div><div><h3>Results</h3><div>A total of 34 studies involving 3655 participants were included. Among them, 29 RCTs showed a low to high risk of bias, while 5 quasi-experimental studies had moderate risk. A network meta-analysis revealed that for NPS, resistance exercise (<em>SMD</em> = −1.70, <em>95 % CI</em>: −3.12 to −0.29) ranked first with 91.8 %; for cognition function, multi-component exercise (<em>SMD</em> = 1.45, <em>95 % CI</em>: −0.56 to –3.47) ranked first with 80.2 %; for quality of daily life (QoL), aerobic exercise (<em>SMD</em> = 0.37, <em>95 % CI</em>: −0.26 to –0.99) ranked first with 77.5 %; and for activities of daily living (ADL), finger exercise (<em>SMD</em> = 0.86, <em>95 % CI</em>: 0.02 to –1.71) ranked first with 89.6 %.</div></div><div><h3>Conclusions</h3><div>This network meta-analysis suggests that resistance exercise is most likely the optimal intervention for improving NPS among older adults with MCI or dementia, while finger exercise appears most effective for enhancing ADL. However, due to the limited number of studies on resistance exercise, these findings should be interpreted with caution, and further high-quality research is needed to confirm its efficacy.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102890"},"PeriodicalIF":12.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988399","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
Tailoring the biomarkers of Alzheimer’s disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives 使用以肠道微生物组为中心的方法定制阿尔茨海默病的生物标志物:临床前,临床和监管观点
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-09-01 DOI: 10.1016/j.arr.2025.102888
Siya Sharma , Bushra Bashir , Kaustubh Ajit Kolekar , Anuradha Acharya , Mukta Gupta , Radheshyam Jena , Sukriti Vishwas , Jaskiran Kaur , Gaurav Gupta , Popat S. Kumbhar , Deepshikha Patle , MVNL Chaitanya , Monica Gulati , Sachin Kumar Singh
{"title":"Tailoring the biomarkers of Alzheimer’s disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives","authors":"Siya Sharma ,&nbsp;Bushra Bashir ,&nbsp;Kaustubh Ajit Kolekar ,&nbsp;Anuradha Acharya ,&nbsp;Mukta Gupta ,&nbsp;Radheshyam Jena ,&nbsp;Sukriti Vishwas ,&nbsp;Jaskiran Kaur ,&nbsp;Gaurav Gupta ,&nbsp;Popat S. Kumbhar ,&nbsp;Deepshikha Patle ,&nbsp;MVNL Chaitanya ,&nbsp;Monica Gulati ,&nbsp;Sachin Kumar Singh","doi":"10.1016/j.arr.2025.102888","DOIUrl":"10.1016/j.arr.2025.102888","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut–brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and evaluates the therapeutic potential of gut-based interventions such as probiotics, prebiotics, synbiotics, metabiotics, postbiotics, and fecal microbiota transplantation (FMT) in mitigating disease pathology. Emphasis has also been given on role of miRNA released from FMT in management of AD. Preclinical and clinical studies demonstrate that these strategies can restore microbial homeostasis, reduce neuroinflammation, enhance gut barrier integrity, and improve cognitive outcomes. The regulatory aspects with use of probiotics based products and FMT is also highlighted. The modulation of neuroimmune, neuroendocrine, and neural pathways through microbiota-derived metabolites offers a promising avenue for AD management. Despite encouraging findings, further research is needed to address interindividual microbiome variability, delivery challenges, and the requirement for large-scale, randomized trials. Personalized gut-targeted approaches may open new horizons for the prevention and treatment of AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102888"},"PeriodicalIF":12.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988402","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
HIV infection is associated with accelerated epigenetic ageing: A systematic review HIV感染与加速表观遗传衰老有关:系统综述
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-28 DOI: 10.1016/j.arr.2025.102884
Mateusz Bożejko , Brygida Knysz , Anna Czernicka , Ignacy Tarski , Aleksandra Szymczak , Małgorzata Małodobra-Mazur
{"title":"HIV infection is associated with accelerated epigenetic ageing: A systematic review","authors":"Mateusz Bożejko ,&nbsp;Brygida Knysz ,&nbsp;Anna Czernicka ,&nbsp;Ignacy Tarski ,&nbsp;Aleksandra Szymczak ,&nbsp;Małgorzata Małodobra-Mazur","doi":"10.1016/j.arr.2025.102884","DOIUrl":"10.1016/j.arr.2025.102884","url":null,"abstract":"<div><h3>Purpose</h3><div>We conducted a systematic review of studies comparing the intensity of epigenetic ageing in people living with human immunodeficiency virus (HIV) and uninfected individuals. We included studies that quantitatively examined the intensity of age-related epigenetic changes in both groups.</div></div><div><h3>Results</h3><div>We identified 25 studies meeting the inclusion criteria. The results of the vast majority (22 out of 25) of the studies included in the review indicate the presence of accelerated epigenetic ageing in people living with HIV compared to uninfected individuals. Most studies reported evidence of epigenetic age acceleration in people living with HIV, both among those not receiving antiretroviral therapy (ART) and those who were on ART treatment. However, the studies included in the review were conducted mostly on relatively small groups and using different methods. While several studies have carefully addressed confounding variables, others did not report adjustments for factors such as BMI, diabetes, HBV and HCV co-infections, or lifestyle influences, which may be especially relevant for interpreting second-generation epigenetic clocks such as GrimAge and PhenoAge.</div></div><div><h3>Conclusions</h3><div>We believe that the results of our review indicate accelerated epigenetic ageing in people living with HIV compared to uninfected individuals. There is a need for further research, which will analyse material from different tissues and take into account a number of biomarkers and the mentioned confounding factors. Studies considering the impact of individual classes of antiretroviral drugs, the age of the patient at the time of HIV diagnosis, and the timeliness of diagnosis on epigenetic ageing are particularly needed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102884"},"PeriodicalIF":12.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913072","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
Unravelling neuronal death mechanisms: The role of cytokines and chemokines in immune imbalance in Alzheimer’s disease progression 揭示神经元死亡机制:细胞因子和趋化因子在阿尔茨海默病进展中免疫失衡的作用
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-28 DOI: 10.1016/j.arr.2025.102883
Sneha Kumari , Rishika Dhapola , Prajjwal Sharma , Mohit Paidlewar , Balachandar Vellingiri , Bikash Medhi , Dibbanti HariKrishnaReddy
{"title":"Unravelling neuronal death mechanisms: The role of cytokines and chemokines in immune imbalance in Alzheimer’s disease progression","authors":"Sneha Kumari ,&nbsp;Rishika Dhapola ,&nbsp;Prajjwal Sharma ,&nbsp;Mohit Paidlewar ,&nbsp;Balachandar Vellingiri ,&nbsp;Bikash Medhi ,&nbsp;Dibbanti HariKrishnaReddy","doi":"10.1016/j.arr.2025.102883","DOIUrl":"10.1016/j.arr.2025.102883","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is marked by neuroinflammation, neurodegeneration and cognitive decline, with emerging evidence highlighting the critical roles of cytokines and chemokines in its pathogenesis. Regulated cell death is a highly structured and meticulously coordinated series of molecular and signalling processes involving gene expression and protein activity. This mechanism is essential for normal developmental processes and the preservation of tissue homeostasis. Abnormal regulation of inflammatory mediators contributes to or results from amyloid-β and tangle deposition, triggers oxidative stress, excitotoxicity, and neuroinflammation, leads to cell death through multiple mechanisms, including apoptosis, ferroptosis, pyroptosis, PANoptosis, etc. The pathogenetic mechanisms responsible for neuronal death and dysfunction in AD are not yet fully understood. This review seeks to compile evidence for the various modes of neuronal cell death in AD and to explore how the neuroinflammatory environment of the AD brain influences these distinct forms of cell death. Several inflammatory signalling cascades are involved in above discussed neuronal death mechanisms, such as RAGE<strong>/</strong>NF-κB, NLRP3 inflammasome, AMPK/mTOR/ULK1, cGAS-STING, RIPK1/RIPK3/MLKL<strong>,</strong> GPX4/Nrf2 and JAK-STAT pathways. Therapeutic drugs such as Magnolol, Necrostatin-1, Salidroside, Azeliragon, DNL788, Baricitinib, Sargramostim, etc. targeting neuroinflammation-associated signaling pathways, have shown efficacy in preclinical and clinical studies mitigating AD pathology. Enhancing our comprehension of neuronal death mechanisms could elucidate disease pathogenesis, offer insights for therapeutic approaches, and aid in developing modified animal models of AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102883"},"PeriodicalIF":12.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913073","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
Vesicle-guided mitochondria: A new perspective for brain mitochondrial transplantation 囊泡引导线粒体:脑线粒体移植的新视角
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-26 DOI: 10.1016/j.arr.2025.102881
Antonella Girgenti , Laura Palumbo , Gokhan Burcin Kubat , Ibrahim Turkel , Pasquale Picone , Domenico Nuzzo
{"title":"Vesicle-guided mitochondria: A new perspective for brain mitochondrial transplantation","authors":"Antonella Girgenti ,&nbsp;Laura Palumbo ,&nbsp;Gokhan Burcin Kubat ,&nbsp;Ibrahim Turkel ,&nbsp;Pasquale Picone ,&nbsp;Domenico Nuzzo","doi":"10.1016/j.arr.2025.102881","DOIUrl":"10.1016/j.arr.2025.102881","url":null,"abstract":"<div><div>Mitochondrial activity is essential for the proper functioning of higher brain processes, and its impairment has been linked to a wide range of neurological disorders. Increasing evidence shows that under physiological and pathological conditions, mitochondria can be secreted into the extracellular environment to regulate various biological responses, including cellular bioenergetics. Today, the therapeutic modality known as “mitochondrial transplantation” has emerged as a cutting-edge and highly promising intervention for the promotion of cell and tissue regeneration. This innovative approach entails the replacement of dysfunctional mitochondria in the recipient organism with healthy, functional exogenous mitochondria, thereby aiming to restore cellular function and promote tissue repair and recovery. Several studies have demonstrated the beneficial effects of local or systemic administration of mitochondria on <em>in vitro</em> and <em>in vivo</em> models of brain diseases. We discuss the effect of mitochondrial transplantation in various brain diseases and highlight some critical issues. In this regard, we propose vesicles as a delivery system for both whole mitochondria and mitochondrial components to target cells in the central nervous system. Furthermore, the aim of this review is twofold: firstly, to emphasize the significance of brain mitochondrial transplantation, and secondly, to prompt the scientific community to consider the practical applications of brain mitochondrial transplantation. To this end, the text highlights the as yet unresolved issues and challenges that must be addressed and surmounted if this field is to progress. In conclusion, the authors express their support for the development of new potential therapies for mitochondrial diseases of the central nervous system.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102881"},"PeriodicalIF":12.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913071","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
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