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}
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}
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}
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}
Sayonara Pereira da Silva , Charikleia Lampraki , Tainá dos Santos Rêgo , Paolo Ghisletta , Matthias Kliegel , Jürgen Maurer , Matthias Studer , Élvio Rúbio Gouveia , Marcelo de Maio Nascimento , Andreas Ihle
{"title":"Can cognitive reserve offset APOE-related Alzheimer’s risk? A systematic review","authors":"Sayonara Pereira da Silva , Charikleia Lampraki , Tainá dos Santos Rêgo , Paolo Ghisletta , Matthias Kliegel , Jürgen Maurer , Matthias Studer , Élvio Rúbio Gouveia , Marcelo de Maio Nascimento , Andreas Ihle","doi":"10.1016/j.arr.2025.102809","DOIUrl":"10.1016/j.arr.2025.102809","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In this study, we systematically investigated research that explored the interaction between <em>APOE</em>-related AD outcomes and CR. The literature search was conducted using PubMed and all Web of Science databases. We screened 33,861 references, of which 15 met the inclusion criteria. The studies varied in research design, population characteristics, proxies for CR, and measured outcomes. The publications presented mixed results, with some indicating protective effects (n = 7), others showing detrimental effects (n = 4), and still others suggesting no significant interaction effects (n = 4). Some of these findings may be attributed to the reliance on individual proxies, which may capture only limited aspects or different dimensions of the broader CR framework. Overall, our analysis suggests that individual risk factors may interact in complex ways and that even genetic predispositions can potentially be influenced by CR. Implications for CR and aging research as well as public health policies are discussed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102809"},"PeriodicalIF":12.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313848","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":"Traditional Chinese herbal medicines for the treatment of ischemic stroke in China","authors":"Xiaomeng Dong , Tianya Zhang , Cong Zhang , Wenyan Shang , Yuqing Zhang , Xiangjian Zhang","doi":"10.1016/j.arr.2025.102803","DOIUrl":"10.1016/j.arr.2025.102803","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a devastating disease with high disability and mortality rates worldwide. Despite advances in medical treatment, managing IS remains a significant challenge. In China, traditional Chinese herbal medicines (TCHMs) are often sought as alternative pharmacotherapies for both prevention and rehabilitation because of their proven efficacy and relatively low incidence of adverse reactions. While TCHMs do have certain limitations, their value cannot be overlooked. Centuries of clinical experience in China have established TCHMs as promising approaches for improving clinical outcomes and accelerating drug discovery in the treatment of IS. In this review, we summarize the potential mechanisms and clinical evidence of TCHMs in the treatment of IS in China. These findings suggest that TCHMs can treat IS through various pharmacological mechanisms, mainly anti-inflammatory, antiapoptotic, antioxidative stress, and mitochondrial regulatory mechanisms. Additionally, TCHMs provide protection to the blood-brain barrier, inhibit excitotoxicity, promote angiogenesis, reduce ferroptosis, modulate the gut-brain axis, prevent thrombosis, improve blood rheology, and regulate neural stem cells. These effects contribute to improved therapeutic outcomes at various stages of IS and poststroke complications, especially when combined with Western medicine, while also offering a favorable safety profile. In conclusion, TCHMs represent a promising strategy for managing IS and advancing related drug development. We hope that this review will inspire further exploration into the mechanisms underlying the anti-IS effects of TCHMs, thereby enhancing the scientific understanding of traditional Chinese medicine.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102803"},"PeriodicalIF":12.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295484","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}
Junzhi Liang , Shurui Gai , Xinni Na , Jia Hu , Zhongyu Zhao , Duo Zi , Zhijing Na , Wenyan Gao , Fangfang Bi , Da Li
{"title":"Ovarian aging at single-cell resolution: Current paradigms and perspectives","authors":"Junzhi Liang , Shurui Gai , Xinni Na , Jia Hu , Zhongyu Zhao , Duo Zi , Zhijing Na , Wenyan Gao , Fangfang Bi , Da Li","doi":"10.1016/j.arr.2025.102807","DOIUrl":"10.1016/j.arr.2025.102807","url":null,"abstract":"<div><div>Ovarian failure is a key event in female reproductive aging, resulting in the depletion of follicular reserve and a decline in fertility. In addition, it triggers systemic pathological changes, including osteoporosis and cardiovascular disease, due to decreased estrogen levels. Despite extensive study, mapping senescent ovarian cells is challenging due to the multicellular composition and heterogeneity of the ovary. In the past decade, single-cell resolution technologies have provided new insights into ovarian aging by enabling the molecular characterization of individual cells. Here, we comprehensively review the application of these technologies in delaying ovarian aging and promoting reproductive health. We summarize their value in uncovering cell-type-specific mechanisms and their potential uses in the research of ovarian aging, ultimately deepening our understanding of its pathogenesis and molecular basis.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102807"},"PeriodicalIF":12.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318927","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 role of microRNAs in the pathophysiology of the aging eye","authors":"Mohammadsaber Tamaddon , Mohammadreza Fazel , Delsuz Rezaee , Mohammad Amin Khalilzad , Jamal Majidpoor , Hamid Ahmadieh , Mohammad-Davood Fattahi , Kosar Namakin , Fatemeh Suri , Sajad Najafi","doi":"10.1016/j.arr.2025.102805","DOIUrl":"10.1016/j.arr.2025.102805","url":null,"abstract":"<div><div>The human eye is a complex organ integral to visual perception, comprising multiple structures, including the retina, cornea, and lens. Vision loss affects over 2.2 billion individuals globally, with conditions, such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy, recognized as responsible for a majority of visual-impairing conditions. Recent research highlights the critical roles of microRNAs (miRNAs)—small non-coding RNAs involved in post-transcriptional gene regulation—in ocular physiology and pathophysiology. miRNAs regulate gene expression by binding to target mRNA, modulating multiple processes like cell growth, apoptosis, and differentiation. Dysregulation of miRNAs has been implicated in various age-related ocular disorders like retinopathy, glaucoma and age-related macular degeneration, thereby disrupting cellular homeostasis and promoting disease progression. Experimental evidence, primarily from murine models, reveals that miRNAs regulate photoreceptor differentiation, retinal development, and the survival of postmitotic retinal cells. Additionally, miRNA dysregulation offers potential diagnostic and therapeutic insights. This study explores the roles of miRNAs in ocular pathophysiology, emphasizing their involvement in the maintenance of retinal cell integrity and visual system homeostasis. Furthermore, the significance of miRNAs in the pathogenesis of various human ophthalmic diseases associated with advancing age is reviewed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102805"},"PeriodicalIF":12.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310931","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}
Ziliang Hao , Jing Du, Xinhao Ding, Yu Shi, Zhiyuan Wang
{"title":"Effectiveness of community-based health education on modifiable risk factors for Alzheimer's disease among older adults: a scoping review","authors":"Ziliang Hao , Jing Du, Xinhao Ding, Yu Shi, Zhiyuan Wang","doi":"10.1016/j.arr.2025.102800","DOIUrl":"10.1016/j.arr.2025.102800","url":null,"abstract":"<div><div>A scoping review of community health education studies for dementia prevention was conducted to clarify the form, content, outcome indicators, evaluation tools, and effects of community health education interventions for dementia prevention and to inform future research in this area. This scoping review of community-based health education interventions for Alzheimer's disease prevention across eight databases identified five intervention approaches—culturally adapted interventions, health knowledge lectures, mental health education, multidimensional comprehensive intervention, and telephone coaching. These interventions primarily aimed to enhance AD knowledge and lifestyle modifications while evaluating outcomes across nine domains including knowledge level, cognitive functioning, attitudinal beliefs, psychological status, health behaviors, health status, life quality, self-management, and other indicators. The findings demonstrated significant improvements in dementia knowledge, increased adoption of protective behaviors, and particularly strong effects in collectivist cultural settings. Most notably, multimodal interventions showed synergistic benefits for both cognitive performance and community health aging outcomes. While current evidence supports the feasibility and effectiveness of community-based health interventions across age groups, large-scale randomized controlled trials incorporating geroscience principles are needed to establish causal efficacy in Alzheimer's prevention and optimize evidence-based intervention frameworks for diverse populations.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102800"},"PeriodicalIF":12.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310930","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}
Siti Masfiah , Alfarid Kurnialandi , Johannes Jacobus Meij , Andrea Britta Maier
{"title":"Definitions of healthspan: A systematic review","authors":"Siti Masfiah , Alfarid Kurnialandi , Johannes Jacobus Meij , Andrea Britta Maier","doi":"10.1016/j.arr.2025.102806","DOIUrl":"10.1016/j.arr.2025.102806","url":null,"abstract":"<div><div>The term healthspan has been widely used in academic literature, technical reports and brochures, however, it is unclear if the same definitions and operationalizations for healthspan are being used. The objective of the systematic review (registration number CRD42023404872) was to summarize definitions of healthspan and their operationalization searching using four databases: PubMed, Embase, Web of Science, and Scopus. Out of 14,551 records, 207 records met the inclusion criteria and 187 articles gave a definition of healthspan. Of these, 113 definitions were considered primary definitions, which refer to an authors' definition without referencing other definitions. Healthspan definitions varied widely, describing the absence of various disease and or disability and were operationalized by measuring the onset of chronic diseases, disability or performance limitations. Two definitions included subjective measures, such as quality of life. In conclusion, definitions of healthspan and their operationalization are not standardized, hampering comparisons of data. A consensus on the definition and operationalization of healthspan is urgently needed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102806"},"PeriodicalIF":12.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310929","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}