Ageing Research Reviews最新文献_第8页

Evaluating effectiveness and implementation of digital health interventions for older adults with cognitive frailty: A systematic review and meta-analysis 评估老年人认知衰弱的数字健康干预的有效性和实施：系统回顾和荟萃分析。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-30 DOI: 10.1016/j.arr.2025.102819

Yanyan Li , Meijun Liu , Jieru Yang , Qinqin Liu , Wendie Zhou , Jiaqi Yu , Xue Wang , Cuili Wang

{"title":"Evaluating effectiveness and implementation of digital health interventions for older adults with cognitive frailty: A systematic review and meta-analysis","authors":"Yanyan Li , Meijun Liu , Jieru Yang , Qinqin Liu , Wendie Zhou , Jiaqi Yu , Xue Wang , Cuili Wang","doi":"10.1016/j.arr.2025.102819","DOIUrl":"10.1016/j.arr.2025.102819","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effectiveness and implementation of digital health interventions compared with control group for older adults with cognitive frailty.</div></div><div><h3>Methods</h3><div>We conducted a systematic review of randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs), searching ten electronic databases and grey literature sources from their inception to 17 March 2024, with an update performed on 15 March 2025. The standardized mean difference (SMD) with 95 % <em>CIs</em> was calculated. The methodological quality was assessed by the Cochrane RoB2 and ROBINS-I.</div></div><div><h3>Results</h3><div>Eleven RCTs and two NRSIs with a total of 1069 participants were included. The meta-analysis showed that the digital health intervention among older adults with cognitive frailty significantly increased global cognitive function (SMD = 0.58, 95 %<em>CI</em> = 0.32, 0.83, <em>P</em> < 0.001), executive function (SMD = −0.54, 95 %<em>CI</em> =-0.99, −0.09, <em>P</em> = 0.02) and physical domain of quality of life (PCS) (SMD = 0.30, 95 %<em>CI</em> = 0.06, 0.55, <em>P</em> = 0.01), and decreased frailty (SMD = −0.41, 95 %<em>CI</em> = −0.81, −0.01, <em>P</em> = 0.04), depressive symptom (SMD =-0.41, 95 %<em>CI</em> =-0.73, −0.08, <em>P</em> = 0.01). RoB2 assessment revealed that six RCTs were rated as high risk, four as low risk, and one as some concerns. Additionally, two NRSIs were assessed as moderate risk using the ROBINS-I tool.</div></div><div><h3>Conclusions</h3><div>Digital health interventions targeting older adults with cognitive frailty have demonstrated effectiveness in improving cognitive function, mental health, and PCS, as well as reducing frailty. High-quality research is warranted to bolster the evidence in these fields in the future.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102819"},"PeriodicalIF":12.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556134","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

Targeting autophagy in doxorubicin-induced cardiotoxicity: A comprehensive review of scientific landscapes and therapeutic innovations 靶向自噬在阿霉素诱导的心脏毒性：科学景观和治疗创新的综合综述

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-28 DOI: 10.1016/j.arr.2025.102818

Shiqi Wang , Lu Wang , Hongxin Cheng , Hanbin Li , Qing Zhang , Chengqi He , Chenying Fu , Quan Wei

{"title":"Targeting autophagy in doxorubicin-induced cardiotoxicity: A comprehensive review of scientific landscapes and therapeutic innovations","authors":"Shiqi Wang , Lu Wang , Hongxin Cheng , Hanbin Li , Qing Zhang , Chengqi He , Chenying Fu , Quan Wei","doi":"10.1016/j.arr.2025.102818","DOIUrl":"10.1016/j.arr.2025.102818","url":null,"abstract":"<div><div>Doxorubicin (DOX)-induced cardiotoxicity (DIC) poses a major threat to elderly cancer patients, often leading to severe cardiac dysfunction and complicating the outcome of cancer treatment. Autophagy is one of the core mechanisms of DIC and is considered a key therapeutic target. We analyzed the status of research in the field of autophagy in DIC via bibliometric methods. A total of 292 publications related to this topic were identified and included. Furthermore, based on included publications and relevant studies in the field of geriatrics, the characteristics of autophagy in the aging heart and DIC, therapeutic strategies targeting autophagy, and challenges in clinical translation were summarized. Our review reveals that research hotspots in the field focus on how to balance the relationship between the effects of cancer treatment and cardiotoxicity, and the frontiers focus on exploring new therapeutic strategies via autophagy regulation. The autophagy ability of aging hearts is significantly reduced, which accelerates the occurrence of myocardial fibrosis, systolic dysfunction, and chronic inflammation. Autophagy has significant bidirectional regulatory effects on DIC. Additionally, the dynamic regulation of autophagy is significantly affected by dose gradients of DOX, exposure time windows, experimental models, and differences in administration methods. Drugs such as dexrazoxane and melatonin, as well as rehabilitation therapies such as aerobic training and resistance training, can regulate cardiomyocyte autophagy and have clinical translational potential. However, age heterogeneity in existing clinical studies undermines the generalizability of findings to elderly cancer patients. Future therapeutic optimization requires regimen customization based on elderly specific organ function decline patterns.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102818"},"PeriodicalIF":12.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518810","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

Exerkines: Potential regulators of diabetic cardiomyopathy 运动因子：糖尿病性心肌病的潜在调节因子。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-28 DOI: 10.1016/j.arr.2025.102816

Fengzhi Yu , Boyi Zong , Zhenjun Tian , Dandan Jia , Ru Wang

{"title":"Exerkines: Potential regulators of diabetic cardiomyopathy","authors":"Fengzhi Yu , Boyi Zong , Zhenjun Tian , Dandan Jia , Ru Wang","doi":"10.1016/j.arr.2025.102816","DOIUrl":"10.1016/j.arr.2025.102816","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM) is a significant contributor to diabetes-related mortality, manifesting through progressive diastolic dysfunction, cardiomyocyte apoptosis, and pathological fibrotic remodeling. While exercise is advocated as a therapeutic intervention for DCM, the molecular basis of its cardioprotective effects remains incompletely understood, particularly regarding systemic interorgan communication mediated by exercise-induced signaling factors. Emerging evidence highlights exerkines, a class of peptides and nucleic acids secreted by skeletal muscle (myokines), adipose tissue (adipokines), bone (osteokines), liver (hepatokines), and other organs in response to physical exercise-as key regulators of DCM pathogenesis. This review systematically examines the cardioprotective potential of exerkines in mitigating functional and structural myocardial impairments characteristic of DCM. The primary focus of this study is to elucidate the mechanisms through which exerkines modulate critical pathophysiological processes, including myocardial oxidative stress, calcium homeostasis dysregulation, programmed cell death, maladaptive renin-angiotensin-aldosterone system activation, endoplasmic reticulum stress, inflammatory signaling, and mitochondrial dysfunction. By synthesizing current understanding of exerkines-mediated cross-tissue communication, this analysis provides novel insights into exercise-based therapeutic strategies targeting the multifaceted pathophysiology of DCM.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102816"},"PeriodicalIF":12.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531605","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

Emerging uncertainty on the anti-aging potential of metformin 二甲双胍抗衰老潜力的新不确定性。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-27 DOI: 10.1016/j.arr.2025.102817

Matthew Thomas Keys , Jesper Hallas , Richard A. Miller , Samy Suissa , Kaare Christensen

{"title":"Emerging uncertainty on the anti-aging potential of metformin","authors":"Matthew Thomas Keys , Jesper Hallas , Richard A. Miller , Samy Suissa , Kaare Christensen","doi":"10.1016/j.arr.2025.102817","DOIUrl":"10.1016/j.arr.2025.102817","url":null,"abstract":"<div><div>Metformin is the most commonly prescribed glucose-lowering agent worldwide for the treatment of type II diabetes. Due to evidence of improvements in healthspan and lifespan in model organisms, and mechanistic data relevant to the hallmarks of aging, it has been considered a promising candidate in the search for pharmacological interventions that may attenuate the ageing process in humans. Various epidemiological studies have been influential in generating support for this hypothesis. These include pronounced anticancer and cardioprotective benefits compared to other antidiabetic treatments, and an observation of metformin use in type II diabetes being associated with better survival than that of the general population. Here we discuss recent developments in the evidence underlying the rationale for using metformin to target ageing. We describe the methodological limitations of some of the early and most influential findings and critically assess their scientific follow-up, including replication attempts of key experimental and observational findings, and a range of clinical trials of metformin in individuals without type II diabetes. These developments generally illustrate an emerging uncertainty in the anti-aging potential of metformin.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102817"},"PeriodicalIF":12.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531604","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

Pancreatic β-cell remodeling in health and aging: Lessons from rodents and humans 健康和衰老中的胰腺β细胞重塑：来自啮齿动物和人类的经验教训

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-25 DOI: 10.1016/j.arr.2025.102815

Radwan Darwish , Yasmine Alcibahy , Sangeeta Dhawan , Alexandra E. Butler , Abu Saleh Md Moin

{"title":"Pancreatic β-cell remodeling in health and aging: Lessons from rodents and humans","authors":"Radwan Darwish , Yasmine Alcibahy , Sangeeta Dhawan , Alexandra E. Butler , Abu Saleh Md Moin","doi":"10.1016/j.arr.2025.102815","DOIUrl":"10.1016/j.arr.2025.102815","url":null,"abstract":"<div><div>Pancreatic β-cells are essential for maintaining glucose homeostasis throughout life. Although rodent models have been instrumental in elucidating β-cell biology, notable differences exist between rodents and humans across fetal, postnatal and adult stages. This review provides a comparative analysis of β-cell development, proliferation and regenerative capacity between these two species, highlighting critical divergences that must be considered when translating preclinical findings to human therapies. During fetal development, distinct temporal patterns of hormone expression and islet architecture are observed, with human β-cell maturation extending postnatally. Postnatal β-cell expansion in rodents is driven predominantly by replication, whereas in humans, proliferation peaks within the first two years of life and declines sharply thereafter. Adult human β-cells exhibit limited regenerative capacity compared to rodents, attributed to intrinsic constraints such as elevated expression of cell cycle inhibitors and chromatin remodeling associated with aging. Additionally, key signaling pathways that robustly stimulate β-cell proliferation in rodents are less effective in humans. Understanding these species-specific differences is vital for the development of therapeutic strategies aimed at β-cell preservation and regeneration in diabetes. Here, we emphasize the need for human-relevant models, including stem cell-derived β-cells and pancreatic organoids, to bridge the translational gap. Future research should prioritize uncovering mechanisms that can safely and effectively enhance β-cell mass in humans, acknowledging the distinct biological landscape that aging imposes on human pancreatic β-cells.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102815"},"PeriodicalIF":12.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502175","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

Cellular senescence in chronic obstructive pulmonary disease: Molecular mechanisms and therapeutic interventions 慢性阻塞性肺疾病的细胞衰老：分子机制和治疗干预

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-24 DOI: 10.1016/j.arr.2025.102813

Sapana Subedi , Mounika Guntipally , Newton Suwal , Rajan Thapa , Saroj Bashyal , Nisha Panth , Gaurav Gupta , Ronan MacLoughlin , Brian Oliver , Kamal Dua , Keshav Raj Paudel

{"title":"Cellular senescence in chronic obstructive pulmonary disease: Molecular mechanisms and therapeutic interventions","authors":"Sapana Subedi , Mounika Guntipally , Newton Suwal , Rajan Thapa , Saroj Bashyal , Nisha Panth , Gaurav Gupta , Ronan MacLoughlin , Brian Oliver , Kamal Dua , Keshav Raj Paudel","doi":"10.1016/j.arr.2025.102813","DOIUrl":"10.1016/j.arr.2025.102813","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is the world's fourth highest reason for mortality, accounting for 3.5 million deaths in 2021, and about 5 % of total global deaths. Emphysema and chronic bronchitis are the two major pathologies of COPD. Tobacco smoke, dust, vapors, and fumes, outdoor air pollutants, genetic factors, ageing, infections, and asthma are the risk factors of COPD. On the other hand, senescence is permanent halt in cell cycle accompanied by phenotypic alterations due to ageing, oxidative stress like; irreparable DNA damage, telomere shortening, oncogene activation or inactivation of tumor suppressors. COPD is often considered an accelerated ageing process of the lungs, with senescent cells impairing tissue repair and regeneration, causing progressive lung function decline. Although, cellular senescence is seen as powerful defense against risk of carcinogenesis in COPD as it arrests cell proliferation irreversibly, excessive collection of senescent cells releases senescence-associated secretory phenotype (SASP) that increase oxidative stress to lungs and leads to long-term inflammation, tissue damage, and hindered lung recovery. This review will address the accelerated ageing process and cellular senescence in COPD, therapeutic approaches targeting senescence regulation in COPD; clinical research and trial studies demonstrating the use of therapies aimed at senescence in COPD along with current obstacles and potential solutions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102813"},"PeriodicalIF":12.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502182","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

Crosstalk between oxidative stress, mitochondrial dysfunction, chromosome instability, and the activation of the cGAS-STING/IFN pathway in systemic sclerosis 系统性硬化症中氧化应激、线粒体功能障碍、染色体不稳定性和cGAS-STING/IFN通路激活之间的串扰

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-23 DOI: 10.1016/j.arr.2025.102812

Mohammad Waseem , Azait Imtiaz , Amanda Alexander , Lauren Graham , Rafael Contreras-Galindo

{"title":"Crosstalk between oxidative stress, mitochondrial dysfunction, chromosome instability, and the activation of the cGAS-STING/IFN pathway in systemic sclerosis","authors":"Mohammad Waseem , Azait Imtiaz , Amanda Alexander , Lauren Graham , Rafael Contreras-Galindo","doi":"10.1016/j.arr.2025.102812","DOIUrl":"10.1016/j.arr.2025.102812","url":null,"abstract":"<div><div>Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis, vascular dysfunction, and immune dysregulation. Recent studies have highlighted the crucial role of cellular stress responses and their connection to innate immunity in SSc pathogenesis, particularly the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, which has emerged as a pivotal mediator. In SSc, cGAS detects cytosolic DNA and activates STING, triggering type I interferon production and proinflammatory responses. Errors in chromosome segregation, leading to chromosomal instability (CIN) and micronucleus formation, are major contributors to cytosolic DNA release. Additionally, mitochondrial dysfunction in response to stress signaling leads to the release of mitochondrial DNA (mtDNA) into the cytoplasm, further enhancing cGAS-STING activation, although this mechanism requires further validation. Furthermore, mitochondrial impairment leads to excessive production of reactive oxygen species (ROS), which cleave chromosomal DNA and oxidize mtDNA, contributing to chronic inflammation and fibrosis. Alterations in inflammasome and endosome pathways further amplify interleukin and type I interferon responses. This review highlights the crosstalk between mitochondria, ROS, chromosomal missegregation, and the cGAS-STING pathway in SSc pathogenesis. We also discuss emerging therapeutics targeting the cGAS-STING pathway, which hold promise for regulating disease progression and improving outcomes for SSc patients. Although most evidence remains preclinical and long-term outcome data are scarce, this review underscores the potential of emerging therapeutic strategies and emphasizes the importance of personalized approaches. Further research into the molecular signatures of this pathway in SSc could pave the way for precision medicine strategies in the clinical management of this disease.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102812"},"PeriodicalIF":12.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480516","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

Association between the inflammageing biomarkers and clinical outcomes amongst the community-dwelling middle-aged and older adults: A systematic review and meta-analysis 在社区居住的中老年人中，炎症生物标志物与临床结果之间的关系：一项系统回顾和荟萃分析

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-23 DOI: 10.1016/j.arr.2025.102811

Delphine Chen , Wilson Wai San Tam , Jinghua Zhang , Jinhua Lu , Vivien Xi Wu

{"title":"Association between the inflammageing biomarkers and clinical outcomes amongst the community-dwelling middle-aged and older adults: A systematic review and meta-analysis","authors":"Delphine Chen , Wilson Wai San Tam , Jinghua Zhang , Jinhua Lu , Vivien Xi Wu","doi":"10.1016/j.arr.2025.102811","DOIUrl":"10.1016/j.arr.2025.102811","url":null,"abstract":"<div><h3>Background</h3><div>Inflammageing biomarkers have been implicated in frailty among middle-aged and older adults. However, there is a paucity of information regarding inflammageing biomarkers association with adverse clinical outcomes, particularly when it is elevated. Understanding this knowledge may allow clinicians to utilise these biomarkers to provide early preventive strategies. This review investigated the association between the elevated inflammageing biomarkers namely C-Reactive Proteins (CRP) including High-Sensitivity (Hs)-CRP, Interleukin-6 (IL-6) and TNF-α (TNF-α) in community-dwelling adults aged 40 years and above on the outcomes of the risk of all-cause mortality, risk of all-cause hospitalisation and risk of all-cause re-admission. Secondary outcomes included risk of depression and anxiety.</div></div><div><h3>Method</h3><div>Studies were searched in PubMed, Embase, Biosis Preview, Web of Science, Scopus and ProQuest Dissertations and Theses along with grey literature. A total of 22 cohort studies were included for analysis. Experimental, quasi-experimental, cross-sectional and case-control studies were excluded.</div></div><div><h3>Results</h3><div>Community-dwelling adults aged 40 years and above have a significantly higher risk of all-cause mortality by 1.54 times and by 1.47 times with elevated CRP/Hs-CRP and elevated IL-6 respectively (p = 0.001; p = 0.001). Those with elevated CRP/Hs-CRP has significantly higher odds of depression by 1.48 times (p < 0.001). Limited evidence exists pertaining to the effect of the inflammageing biomarkers on the risk of hospitalisation, risk of re-admission and risk of anxiety.</div></div><div><h3>Conclusion</h3><div>Precision care interventions of biomarkers monitoring implemented into chronic disease follow-up on the CRP or Hs-CRP as well as IL-6 levels may reduce the risk of mortality and depression.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102811"},"PeriodicalIF":12.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499798","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 potential role of aryl hydrocarbon receptor in Alzheimer's disease: Protective or detrimental 芳烃受体在阿尔茨海默病中的潜在作用：保护或有害

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-17 DOI: 10.1016/j.arr.2025.102810

Hayder M. Al-kuraishy , Thabat J. Al-Maiahy , Ghassan M. Sulaiman , Hamdoon A. Mohammed , Ali K. Albuhadily , Ali I. Al-Gareeb , Mosleh M. Abomughaid

{"title":"The potential role of aryl hydrocarbon receptor in Alzheimer's disease: Protective or detrimental","authors":"Hayder M. Al-kuraishy , Thabat J. Al-Maiahy , Ghassan M. Sulaiman , Hamdoon A. Mohammed , Ali K. Albuhadily , Ali I. Al-Gareeb , Mosleh M. Abomughaid","doi":"10.1016/j.arr.2025.102810","DOIUrl":"10.1016/j.arr.2025.102810","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the main cause of dementia in the old-age population worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce the accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). Particularly, cholinergic neurons in the prefrontal cortex and hippocampus are mainly affected in AD, resulting in cognitive impairment and memory dysfunction. Therefore, restoration of cholinergic neurotransmission by cholinergic agonists such as tacrine and donepezil could be effective in the management of AD. However, anti-AD medications cannot reverse the fundamental AD neuropathology. Therefore, targeting other pathways might be reasonable in the management of AD. Interestingly, aryl hydrocarbon receptors (AHRs), which are sensors for xenobiotics and enterobiotics, are involved in age-related neurodegeneration. It has been shown that AHRs have detrimental effects on AD neuropathology by disruption of BBB integrity and induction of cognitive impairment. Conversely, activation of brain AHRs by tryptophan attenuates the inflammatory reactions in AD. These findings emphasized the controversial roles of AHRs in the pathogenesis of AD. Therefore, this review discusses the exact role of AHRs in AD regarding the molecular mechanisms and related signaling pathways.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102810"},"PeriodicalIF":12.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313847","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

Start the engine of neuroregeneration: A mechanistic and strategic overview of direct astrocyte-to-neuron reprogramming 启动神经再生引擎：直接星形胶质细胞到神经元重编程的机制和策略概述

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2025-06-17 DOI: 10.1016/j.arr.2025.102808

Hangyuan Jiang , Hengxing Qi , Anying Tang , Shaohua Hu , Jianbo Lai

{"title":"Start the engine of neuroregeneration: A mechanistic and strategic overview of direct astrocyte-to-neuron reprogramming","authors":"Hangyuan Jiang , Hengxing Qi , Anying Tang , Shaohua Hu , Jianbo Lai","doi":"10.1016/j.arr.2025.102808","DOIUrl":"10.1016/j.arr.2025.102808","url":null,"abstract":"<div><div>The decline of adult neurogenesis and neuronal function during aging underlies the onset and progression of neurodegenerative diseases such as Alzheimer’s disease. Conventional therapies, including neurotransmitter modulators and antibodies targeting pathogenic proteins, offer only symptomatic improvement. As the most abundant glial cells in the brain, astrocytes outnumber neurons nearly fivefold. However, their proliferative and transdifferentiation potential renders them ideal candidates for in situ neuronal replacement. Direct astrocyte-to-neuron reprogramming offers a promising regenerative approach to restore damaged neural circuits. Herein, we propose a “car start-up” model to conceptualize this process, emphasizing the need to inhibit non-neuronal fate pathways (release the handbrake), suppress transcriptional repressors (release the footbrake), and activate neuron-specific gene expression (step on the gas). Additionally, overcoming metabolic barriers in the cytoplasm is essential for successful lineage conversion. Viral or non-viral vectors deliver reprogramming factors, while small molecules serve as metabolic and epigenetic fuel to boost efficiency. In summary, we review the current evidence supporting direct astrocyte-to-neuron reprogramming as a viable regenerative strategy in the aging brain. We also highlight the conceptual “car start-up” model as a useful framework to dissect the molecular logic of lineage conversion and emphasize its promising therapeutic potential for combating neurodegenerative diseases.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102808"},"PeriodicalIF":12.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313846","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