Ageing Research Reviews最新文献

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Histopathological and ultrastructural changes in different cell types during ischemic and hemorrhagic stroke 缺血性和出血性脑卒中不同细胞类型的组织病理学和超微结构变化。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-07-25 DOI: 10.1016/j.arr.2025.102846
Houlian Zhang , Na Xing , Junmin Wang , Jing Zhang , Cao Jia , Yifei Li , Hualin Fan , Yiying Liu , Fatemeh Dialameh , Nannan Cheng , Yanyan Sun , Junyang Wang , Menglu Wang , Moxin Wu , Xiaoping Yin , Wei Zhu , Jing Li , Jiewen Zhang , Chao Jiang , Fei Xing , Jian Wang
{"title":"Histopathological and ultrastructural changes in different cell types during ischemic and hemorrhagic stroke","authors":"Houlian Zhang ,&nbsp;Na Xing ,&nbsp;Junmin Wang ,&nbsp;Jing Zhang ,&nbsp;Cao Jia ,&nbsp;Yifei Li ,&nbsp;Hualin Fan ,&nbsp;Yiying Liu ,&nbsp;Fatemeh Dialameh ,&nbsp;Nannan Cheng ,&nbsp;Yanyan Sun ,&nbsp;Junyang Wang ,&nbsp;Menglu Wang ,&nbsp;Moxin Wu ,&nbsp;Xiaoping Yin ,&nbsp;Wei Zhu ,&nbsp;Jing Li ,&nbsp;Jiewen Zhang ,&nbsp;Chao Jiang ,&nbsp;Fei Xing ,&nbsp;Jian Wang","doi":"10.1016/j.arr.2025.102846","DOIUrl":"10.1016/j.arr.2025.102846","url":null,"abstract":"<div><div>Stroke is a disease of the central nervous system that leads to high rates of morbidity and mortality, along with limited treatment options. This condition is frequently linked to pathologic alterations at the ultrastructural level within diverse neuronal components, including cell bodies, neurites, and synapses, as well as in glial cells like astrocytes, microglia, and oligodendrocytes. These changes include alterations in the shape and size of cell bodies, disruption of neurites, and changes in the density and distribution of synapses. The blood-brain barrier, a crucial component of the brain's defense system, is also compromised following a stroke, leading to further complications. Although stroke research has significantly advanced, there is still a lack of comprehensive reviews on ultrastructural pathological changes. Given the current challenges in treating stroke, identifying dynamic subcellular structural changes can improve our understanding of the complex pathologic processes after a stroke, ultimately enhancing clinical diagnosis and therapeutic strategies. This review aims to summarize and analyze the ultrastructural changes documented through transmission electron microscopy in both ischemic and hemorrhagic stroke, providing insights for future research and developing novel treatments.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102846"},"PeriodicalIF":12.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sphk2 in ischemic stroke pathogenesis: Roles, mechanisms, and regulation strategies Sphk2在缺血性卒中发病机制中的作用、机制和调控策略
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-07-25 DOI: 10.1016/j.arr.2025.102844
Mengzhao Feng , Qi Qin , Kaiyuan Zhang , Fang Wang , Dengpan Song , Mengyuan Li , Yuan An , Zhihua Li , Fuyou Guo
{"title":"Sphk2 in ischemic stroke pathogenesis: Roles, mechanisms, and regulation strategies","authors":"Mengzhao Feng ,&nbsp;Qi Qin ,&nbsp;Kaiyuan Zhang ,&nbsp;Fang Wang ,&nbsp;Dengpan Song ,&nbsp;Mengyuan Li ,&nbsp;Yuan An ,&nbsp;Zhihua Li ,&nbsp;Fuyou Guo","doi":"10.1016/j.arr.2025.102844","DOIUrl":"10.1016/j.arr.2025.102844","url":null,"abstract":"<div><div>Ischemic stroke, a leading cause of mortality and long-term disability worldwide, is characterized by acute cerebral artery occlusion leading to neuronal death and functional deficits. Despite advances in reperfusion therapies, the lack of effective neuroprotective agents underscores the need for novel therapeutic strategies targeting secondary injury mechanisms. Sphingosine kinase 2 (Sphk2) has emerged as a pivotal regulator in ischemic stroke pathogenesis, mitigating blood-brain barrier leakage, neuroinflammation, and neuronal survival through its downstream metabolite, sphingosine-1-phosphate. This review comprehensively examines the roles and mechanisms of Sphk2 in ischemic stroke, highlighting its potential in anti-inflammation and neuroprotection. We discuss current therapeutic approaches targeting Sphk2, including pharmacological activation, natural compounds and gene therapy. Future directions focus on developing Sphk2-specific agonists, optimizing delivery strategies, and exploring cell type-specific adeno-associated virus vectors and engineered exosomes modulation to maximize therapeutic efficacy while minimizing off-target effects. By synthesizing current knowledge and identifying gaps, this review provides a roadmap for harnessing Sphk2 as a therapeutic target to improve stroke outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102844"},"PeriodicalIF":12.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut-brain relationship in dementia and Alzheimer's disease: Impact on stress and immunity 痴呆和阿尔茨海默病的肠脑关系:对压力和免疫的影响。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-07-23 DOI: 10.1016/j.arr.2025.102843
Upasana Mukherjee , P. Hemachandra Reddy
{"title":"Gut-brain relationship in dementia and Alzheimer's disease: Impact on stress and immunity","authors":"Upasana Mukherjee ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.arr.2025.102843","DOIUrl":"10.1016/j.arr.2025.102843","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is increasingly recognized as a condition shaped not only by central nervous system pathology but also by complex, bidirectional interactions between the gut, brain, and immune system. This review synthesizes emerging evidence on gut-brain-immune dysregulation in AD, with particular attention to how chronic stress, microbial imbalance, and neuroimmune signaling converge to influence disease risk and progression. We move beyond traditional microbiome-focused perspectives to incorporate non-microbial gut-derived mediators, including enteroendocrine hormones, bile acids, and vagal neuropeptides, which contribute to immune modulation, neurotransmission, and brain homeostasis. Importantly, we highlight that AD-related neurodegeneration can also feedback to impair gastrointestinal function and microbial composition, creating a self-reinforcing pathological loop. The review integrates recent findings on the role of host genetic polymorphisms, such as APOE4 and TREM2, in modulating gut permeability, immune tone, and microbiota profiles—emphasizing a systems biology model in which genome-microbiome interactions shape AD susceptibility. We also explore how single-cell omics technologies and multi-organ frameworks are redefining our understanding of gut-brain-immune circuits at cellular resolution. The translational section critically evaluates current and potential therapeutic strategies, including dietary, microbial, behavioral, and endocrine interventions, while addressing the challenges of applying preclinical findings to diverse human populations across the disease spectrum. By incorporating age-, stage-, and genotype-specific considerations, this review offers a comprehensive and timely synthesis of the gut-brain-stress axis in AD, positioning it as a key frontier in mechanistic research and precision therapeutic development.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102843"},"PeriodicalIF":12.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial dysfunction in postoperative cognitive dysfunction: From preclinical mechanisms to multimodal diagnostics and precision intervention 术后认知功能障碍中的线粒体功能障碍:从临床前机制到多模式诊断和精确干预。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-07-23 DOI: 10.1016/j.arr.2025.102845
Fengying Liu , Xiaodong Wu , Zilin Wang , Ao Li , Yuan Luo , Jiangbei Cao
{"title":"Mitochondrial dysfunction in postoperative cognitive dysfunction: From preclinical mechanisms to multimodal diagnostics and precision intervention","authors":"Fengying Liu ,&nbsp;Xiaodong Wu ,&nbsp;Zilin Wang ,&nbsp;Ao Li ,&nbsp;Yuan Luo ,&nbsp;Jiangbei Cao","doi":"10.1016/j.arr.2025.102845","DOIUrl":"10.1016/j.arr.2025.102845","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) poses a significant clinical challenge with far-reaching implications for patient recovery and long-term quality of life. Growing evidence underscores the central role of mitochondrial dysfunction in the pathogenesis of POCD, uncovering an intricate interplay of molecular mechanisms that influence cognitive function. This study reviews the key mechanistic pathways involving mitochondria: bioenergetic impairment and metabolic irregularities, oxidative stress pathways and neuroinflammation, disruptions in calcium signaling, and deficiencies in mitochondrial quality control mechanisms-including kinetic abnormalities, defective mitophagy, and mitochondrial genetic material damage. Each of these pathways acts as a potential molecular nexus contributing to the cognitive decline in post-surgery, revealing the multifaceted nature of POCD progression. Furthermore, the review synthesizes recent advances in diagnostic and preventive strategies targeting mitochondrial dysfunction, bridging preclinical discoveries with clinical relevance. By delineating the role of mitochondria in the molecular landscape of POCD, this review not only clarifies the disease’s pathogenic foundations but also paves the way for future translational research in mitochondria-targeted diagnostics and interventions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102845"},"PeriodicalIF":12.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bidirectional regulation of neuronal autophagy in ischemic stroke: Mechanisms and therapeutic potential 缺血性脑卒中中神经元自噬的双向调节:机制和治疗潜力。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-07-22 DOI: 10.1016/j.arr.2025.102842
Yige Wu , Zhu Li , Tao Ding, Yunqi Yang, Congmin Wei, Shanshan Zhang, Xiang Fan
{"title":"Bidirectional regulation of neuronal autophagy in ischemic stroke: Mechanisms and therapeutic potential","authors":"Yige Wu ,&nbsp;Zhu Li ,&nbsp;Tao Ding,&nbsp;Yunqi Yang,&nbsp;Congmin Wei,&nbsp;Shanshan Zhang,&nbsp;Xiang Fan","doi":"10.1016/j.arr.2025.102842","DOIUrl":"10.1016/j.arr.2025.102842","url":null,"abstract":"<div><div>Ischemic stroke, characterized by cerebral blood flow disruption, triggers complex pathophysiological responses where neuronal autophagy plays a bidirectional regulation role in neuroprotection and injury. Autophagy, activated by energy deprivation, hypoxia, and endoplasmic reticulum stress, dynamically regulates neuronal survival through selective autophagy (e.g., mitophagy, endoplasmic reticulum-phagy, ferritinophagy) of damaged organelles and protein aggregates. Early-stage moderate autophagy exerts neuroprotection by clearing cytotoxic aggregates and maintaining metabolic homeostasis, while excessive or prolonged autophagy exacerbates neuronal death via energy depletion and activation of apoptosis/ferroptosis pathways. Key regulatory mechanisms involve AMPK/mTOR, PI3K/AKT, HIF-1, and MAPK signaling, which modulate autophagic flux and crosstalk with oxidative stress, inflammation, and mitochondrial dynamics. Notably, selective autophagy pathways exhibit spatiotemporal specificity: mitophagy <em>via</em> PINK1/Parkin and BNIP3/FUNDC1 balances mitochondrial quality control, while ferritinophagy-mediated iron dysregulation drives ferroptosis. Pharmacological interventions targeting autophagy-related pathways (e.g., rapamycin, 3-MA, NCOA4 inhibitors) or natural compounds (e.g., Ginkgolide B, HSYA) demonstrate therapeutic potential by fine-tuning autophagic activity. However, challenges remain in defining optimal autophagy thresholds and translating preclinical findings to clinical applications. This review highlights the critical importance of spatiotemporal regulation of neuronal autophagy to develop precise neuroprotective strategies for ischemic stroke, with a particular focus on the interaction between autophagy modulators and the pathophysiological mechanisms of ischemia.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102842"},"PeriodicalIF":12.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The evolution of Alzheimer’s disease: From mitochondria to microglia 阿尔茨海默病的进化:从线粒体到小胶质细胞。
IF 12.5 1区 医学
Ageing Research Reviews Pub Date : 2025-07-21 DOI: 10.1016/j.arr.2025.102838
Feng-ge Yang , Yu-lin Liang , Xu Wang , Jun-ting Wang , Wei Gao , Qiu-yan Ye , Xue-yuan Li , Yu Yang , Hong-lin Li
{"title":"The evolution of Alzheimer’s disease: From mitochondria to microglia","authors":"Feng-ge Yang ,&nbsp;Yu-lin Liang ,&nbsp;Xu Wang ,&nbsp;Jun-ting Wang ,&nbsp;Wei Gao ,&nbsp;Qiu-yan Ye ,&nbsp;Xue-yuan Li ,&nbsp;Yu Yang ,&nbsp;Hong-lin Li","doi":"10.1016/j.arr.2025.102838","DOIUrl":"10.1016/j.arr.2025.102838","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) represents the most prevalent neurodegenerative disorder worldwide. Recent studies highlights that mitochondrial dysfunction drives alterations in microglial function, serving as a pivotal mechanism in the pathogenesis and progression of AD. Increasingly, there is evidence that mitochondrial dysfunction encompasses energy metabolism deficits, heightened oxidative stress, impaired mitochondrial dynamics, disrupted autophagy, and calcium homeostasis imbalances. These impairments modulate microglial activation states, precipitating exacerbated neuroinflammation, altered phagocytic capacity, and increased cellular apoptosis, collectively contributing to microglial dysfunction. This paper presents a narrative review on the relationship between mitochondrial dysfunction and AD, elucidating the impact of mitochondrial impairment on microglia. It summarizes therapeutic strategies that target mitochondria to modulate microglial function, aiming to prevent and treat AD. The goal is to provide new perspectives and insights for AD research and treatment, contributing to improving patients' quality of life and prognosis.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102838"},"PeriodicalIF":12.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Micro/nanoplastic-driven cardiovascular senescence and multi-target intervention by traditional Chinese medicine 微/纳米塑料驱动的心血管衰老及中药多靶点干预。
IF 12.5 1区 医学
Ageing Research Reviews Pub Date : 2025-07-21 DOI: 10.1016/j.arr.2025.102841
Yuan Liu , Yuetong Li , Yue Yin , Lu Yu , Heng Ma
{"title":"Micro/nanoplastic-driven cardiovascular senescence and multi-target intervention by traditional Chinese medicine","authors":"Yuan Liu ,&nbsp;Yuetong Li ,&nbsp;Yue Yin ,&nbsp;Lu Yu ,&nbsp;Heng Ma","doi":"10.1016/j.arr.2025.102841","DOIUrl":"10.1016/j.arr.2025.102841","url":null,"abstract":"<div><div>Micro/nanoplastics (MNPs), pervasive environmental pollutants, accumulate in cardiovascular tissues and drive premature aging through multiscale pathophysiological cascades. This review synthesizes evidence establishing environmental phenotypic aging as a novel mechanistic link between MNP exposure and cardiovascular senescence. MNPs induce mitochondrial damage involving cristae disruption and mtDNA leakage activating cGAS-STING, epigenetic reprogramming encompassing METTL3-mediated m6A hypermethylation and SIRT1/3 suppression, telomere attrition, and NLRP3 inflammasome-dependent inflammaging. It is crucial to note that traditional Chinese medicine (TCM) has been identified as an effective countermeasure. The multi-compound therapeutics of TCM simultaneously target oxidative stress, inflammatory fibrosis, and cell death pathways, thereby restoring cardiovascular homeostasis. By combining environmental toxicology and geroprotection research, this work establishes TCM's holistic approach as a paradigm-shifting intervention against the cardiovascular aging caused by plastic pollution, providing practical strategies to address a mounting public health crisis.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102841"},"PeriodicalIF":12.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700598","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
Advancements in deep learning-based image screening for orthopedic conditions: Emphasis on osteoporosis, osteoarthritis, and bone tumors 基于深度学习的骨科疾病图像筛选研究进展:重点关注骨质疏松症、骨关节炎和骨肿瘤。
IF 12.5 1区 医学
Ageing Research Reviews Pub Date : 2025-07-19 DOI: 10.1016/j.arr.2025.102840
Tian-You Guo , Jin-Hao Deng , Zi-Meng Zhou , Jin-Yuan Chen , Hong-Fa Zhou , Xuan Zhang , Tian-Tian Qi , Hui Zeng , Fei Yu
{"title":"Advancements in deep learning-based image screening for orthopedic conditions: Emphasis on osteoporosis, osteoarthritis, and bone tumors","authors":"Tian-You Guo ,&nbsp;Jin-Hao Deng ,&nbsp;Zi-Meng Zhou ,&nbsp;Jin-Yuan Chen ,&nbsp;Hong-Fa Zhou ,&nbsp;Xuan Zhang ,&nbsp;Tian-Tian Qi ,&nbsp;Hui Zeng ,&nbsp;Fei Yu","doi":"10.1016/j.arr.2025.102840","DOIUrl":"10.1016/j.arr.2025.102840","url":null,"abstract":"<div><div>Artificial intelligence (AI) has garnered increasing attention in the medical field. As the core technology of AI, deep learning (DL) has been extensively applied to the imaging-based screening of orthopedic diseases, primarily including image classification, segmentation, and risk prediction. This review systematically summarizes recent research advances, methodologies, and clinical applications of AI-assisted diagnostic technologies in orthopedic imaging, highlighting the practical value and development trends of DL in this field. By retrieving literature published over the past five years in PubMed and the Web of Science Core Collection, this study emphasizes the application of DL-based techniques in the screening of orthopedic conditions, such as osteoarthritis (OA), osteoporosis (OP), and bone tumors. The results demonstrate that DL-based methods exhibit excellent diagnostic performance and considerable clinical potential. However, despite the rapid increase in research output, there are still several challenges in this field, including the lack of high-quality datasets, the limited cross-institutional generalizability of models, the absence of standardized quality control protocols, and the urgent demand for multicenter clinical validation. Overall, DL holds great promise for enhancing diagnostic accuracy and improving patient outcomes in orthopedic imaging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102840"},"PeriodicalIF":12.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683779","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
Demystifying common DNA methylation sites that promote the ability of CheekAge to associate with health and disease 揭开促进CheekAge与健康和疾病相关能力的常见DNA甲基化位点的神秘面纱
IF 12.5 1区 医学
Ageing Research Reviews Pub Date : 2025-07-19 DOI: 10.1016/j.arr.2025.102839
Adiv A. Johnson, Maxim N. Shokhirev
{"title":"Demystifying common DNA methylation sites that promote the ability of CheekAge to associate with health and disease","authors":"Adiv A. Johnson,&nbsp;Maxim N. Shokhirev","doi":"10.1016/j.arr.2025.102839","DOIUrl":"10.1016/j.arr.2025.102839","url":null,"abstract":"<div><div>We recently showed that the next-generation epigenetic aging clock CheekAge was significantly associated with 33 different health and disease signals across 25 publicly available MethylationEPIC datasets. We additionally uncovered DNA methylation sites that played a disproportionately important role in driving the ability of CheekAge to associate with each of these variables. We dubbed these “pro” CpGs because of their ability to promote a given association. Here, we identify 2639 common DNA methylation sites that were a “pro” CpG for at least two different health and disease signals. Using genes annotated to these common “pro” CpGs, we perform extensive enrichment analyses to unveil motifs of DNA repair, cell division, tumors, cancer, and inherited syndromes. We additionally show that a plethora of genes linked to these common “pro” CpGs have been reported to alter lifespan and/or healthspan in model organisms when manipulated. Some of these were highly germane to canonical signaling pathways, such as <em>RPTOR</em> (encoding for Regulatory-associated protein of mTOR) and <em>FOXA2</em> (encoding for Hepatocyte nuclear factor 3-beta). We also honed in on the seven DNA methylation sites that represented the most common “pro” CpGs, which were cg00005888, cg02478836, cg18331022, cg01892528, cg27634071, cg09232037, and cg17841124. Not only do we summarize available literature for these sites and their annotated genes, but we show that they can be combined into a proof-of-concept epigenetic biomarker that associates with alcohol intake, diet quality, and sex. All together, we provide additional insights into DNA methylation sites that underlie CheekAge’s ability to associate with meaningful signals.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102839"},"PeriodicalIF":12.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680663","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 role of TRIM proteins in chronic inflammation-associated musculoskeletal diseases TRIM蛋白在慢性炎症相关肌肉骨骼疾病中的作用
IF 12.5 1区 医学
Ageing Research Reviews Pub Date : 2025-07-18 DOI: 10.1016/j.arr.2025.102837
Gregory Livshits , Alexander Kalinkovich
{"title":"The role of TRIM proteins in chronic inflammation-associated musculoskeletal diseases","authors":"Gregory Livshits ,&nbsp;Alexander Kalinkovich","doi":"10.1016/j.arr.2025.102837","DOIUrl":"10.1016/j.arr.2025.102837","url":null,"abstract":"<div><div>Musculoskeletal disorders (MSDs), including osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP), and intervertebral disc degenerative disease (IVDD), are among the most common and serious health problems worldwide. However, despite extensive research, drug therapy for these diseases remains a major challenge. This is likely due to a poor understanding of the underlying mechanisms. Recent evidence suggests that the development of these MSDs is associated with protein dysregulation and ongoing chronic inflammation. Protein turnover is controlled by the ubiquitin-proteasome system (UPS), in which E3 ubiquitin ligases, including tripartite motif proteins (TRIMs), are responsible for substrate specificity. Since multiple TRIMs are involved in the development of MSDs, their targeting may be used to correct impaired protein turnover. The recent development of targeted protein degradation technologies has revolutionized drug discovery by selectively degrading specific proteins using the UPS. It is hypothesized that failure to resolve chronic inflammation plays a critical role in the development of MSDs, suggesting that its successful resolution will result in the alleviation of MSD-related symptoms. The process of inflammation resolution is enabled by specialized pro-resolving mediators (SPMs), which are enzymatically generated from dietary essential polyunsaturated fatty acids. Supplementation with SPMs or their stable, small-molecule receptor mimetics and agonists has shown beneficial effects in MSD animal models. In this review, we substantiate the idea that the combined use of TRIM-targeting drugs and inflammation-resolving compounds represents a promising new therapeutic approach to mitigate OA, RA, OP, and IVDD manifestations and improve patient outcomes.</div></div><div><h3>Methods</h3><div>Aligning with the primary objectives of this review, we used a narrative-style review design to explore and critically analyze the potential links between TRIMs, chronic inflammation, and musculoskeletal disorders. Articles included in this review were identified through literature searches using PubMed (English-language original and review articles published until May 2025). The following search terms were used considering all possible combinations: \"TRIM proteins\", \"ubiquitin proteasome system\", \"ubiquitin ligases\", \"targeted protein degradation\", \"proteolytic targeting chimeras\", \"molecular glues\", \"musculoskeletal disorders\", \"osteoarthritis\", “rheumatoid arthritis\", \"osteoporosis\", \"intervertebral disc degenerative disease\", \"chronic inflammation\", \"inflammation resolution\", \"specialized pro-resolving mediators\". Search results were supplemented by reviewing reference citations from the articles identified in the initial searches and drawing on the authors' familiarity with the published literature.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102837"},"PeriodicalIF":12.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676779","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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