Ageing Research Reviews最新文献

{"title":"TREM2 bridges microglia and extracellular microenvironment: Mechanistic landscape and therapeutical prospects on Alzheimer’s disease","authors":"Yiheng Zhao ,&nbsp;Qian Guo ,&nbsp;Jia Tian ,&nbsp;Wei Liu ,&nbsp;Xiaochuan Wang","doi":"10.1016/j.arr.2024.102596","DOIUrl":"10.1016/j.arr.2024.102596","url":null,"abstract":"<div><div>Neuroinflammation is closely related to the pathogenesis of Alzheimer’s disease (AD). One of its prominent cellular components, microglia, is a potent coordinator of neuroinflammation in interplay with the characteristic AD pathological alterations including Aβ, tau, and neuronal defects, which constitute the AD-unique extracellular microenvironment. Mounting evidence implicates Triggering Receptors Expressed on Myeloid Cells 2 (TREM2) in the center of microglial activation, a vital event in the pathogenesis of AD. TREM2 is a pivotal microglial receptor that interacts with specific elements present in the AD microenvironment and induces microglial intracellular signallings contributing to phagocytosis, migration, cytokine production, metabolism, and survival, which shapes the microglial activation profile. It follows that TREM2 builds up a bridge between microglia and the extracellular microenvironment. This review illustrates how TREM2 modulates microglia to affect AD pathogenesis. Mainly presented facets in the review are i. the development of AD-specific microglial phenotypes (disease-associated microglia, DAM), ii. microglial interactions with major AD pathologies, and iii. the underlying intracellular signallings of microglial activation. Also, outstanding controversies regarding the nature of neuroinflammation are discussed. Through our illustration, we attempt to establish a TREM2-centered network of AD pathogenesis, in the hope as well to provide insights into the potential therapeutic strategies based on the underlying mechanisms.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102596"},"PeriodicalIF":12.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752644","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 mitochondrial integrated stress response: A novel approach to anti-aging and pro-longevity","authors":"Xiaoding Wang,&nbsp;Guangyu Zhang","doi":"10.1016/j.arr.2024.102603","DOIUrl":"10.1016/j.arr.2024.102603","url":null,"abstract":"<div><div>The ISR is a cellular signaling pathway that responds to various physiological changes and types of stimulation. The mitochondrial integrated stress response (ISR^mt) is a stress response specific to mitochondria which is initiated by eIF2α phosphorylation and is responsive to mitochondrial stressors. The ISR^mt triggers diverse metabolic responses reliant on activating transcription factor 4 (ATF4). The preliminary phases of ISR^mt can provoke an adaptive stress response that antagonizes age-related diseases and promotes longevity. In this review, we provide an overview of the molecular mechanisms of the ISR^mt, with a particular focus on its potential as a therapeutic target for age-related disease and the promotion of longevity.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102603"},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteosarcopenic adiposity and its relation to cancer and chronic diseases: Implications for research to delineate mechanisms and improve clinical outcomes","authors":"Jasminka Z. Ilich ,&nbsp;Biljana Pokimica ,&nbsp;Danijela Ristić-Medić ,&nbsp;Snjezana Petrović ,&nbsp;Aleksandra Arsić ,&nbsp;Nadja Vasiljević ,&nbsp;Vesna Vučić ,&nbsp;Owen J. Kelly","doi":"10.1016/j.arr.2024.102601","DOIUrl":"10.1016/j.arr.2024.102601","url":null,"abstract":"<div><div>This is the third review in our series examining the connection between osteosarcopenic adiposity/obesity (OSA/OSO) syndrome and health impairments. The objective here was to examine whether there is a causal and/or bidirectional relationship between OSA and some chronic diseases. The search (in PubMed, Scopus, and WoS), screened for articles from their inception to the end of February 2024. Of n=859 articles retrieved, eleven met the eligibility criteria (having all three body composition compartments measured-bone, muscle, adipose tissue and being conducted in adult humans with chronic disease). The selected articles included four assessing OSA and cancers, one each assessing OSA and HIV, Cushing’s disease (CD), chronic kidney disease (CKD), pulmonary function, and two for alcohol abuse-caused liver disease, as well as one 6-year study showing the progression to OSA over time. There was a positive relationship between OSA and each of the chronic diseases, as well as a possible bidirectional relationship between OSA and cancers. The evidence linking OSA with HIV, CD, CKD, liver disease, and pulmonary function, was insufficient to derive firm conclusions about their causal/bidirectional relations. This review emphasizes the need for a multidisciplinary approach in the management and treatment of chronic diseases where body composition assessment should get full attention. To close the knowledge gap, more studies about the role of OSA in chronic diseases are needed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102601"},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747273","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":"Global, regional, and national burden of spinal cord injury from 1990 to 2021 and projections for 2050: A systematic analysis for the Global Burden of Disease 2021 study","authors":"Yubao Lu ,&nbsp;Zhizhong Shang ,&nbsp;Wei Zhang ,&nbsp;Xuchang Hu ,&nbsp;Ruoqi Shen ,&nbsp;Keni Zhang ,&nbsp;Yuxin Zhang ,&nbsp;Liangming Zhang ,&nbsp;Bin Liu ,&nbsp;Mao Pang ,&nbsp;Limin Rong","doi":"10.1016/j.arr.2024.102598","DOIUrl":"10.1016/j.arr.2024.102598","url":null,"abstract":"<div><h3>Objectives</h3><div>Spinal cord injury (SCI) leads to significant functional impairments and mortality, yet outdated epidemiological data hinder effective public health policies. This study utilizes the latest data from the Global Burden of Disease Study 2021 (GBD 2021) to analyze SCI trends and inform prevention strategies.</div></div><div><h3>Methods</h3><div>Using GBD 2021 data, we examined age-standardized incidence, prevalence, and years lived with disability (YLDs) of SCI, along with trends, driving factors, age-sex-time patterns, and projections up to 2050.</div></div><div><h3>Results</h3><div>In 2021, the burden of SCI, including incidence, prevalence, and YLDs, increased with age. However, both prevalence and YLDs exhibited a slight decline after peaking at age 70, with similar trends observed in both males and females. From 1990–2021, the global burden of SCI showed a gradual decline across all populations, including males and females, and it is projected to decrease further by 2050. Nevertheless, significant disparities in disease burden exist between different countries and regions; high-SDI areas experienced a gradual decline after reaching a peak, while low-SDI areas saw a gradual increase from low levels. The primary drivers of this change include population growth and aging, although epidemiological shifts have somewhat alleviated the burden of SCI. The research also indicates that males and older adults, particularly those aged 70 and above, bear the most severe burden of SCI, with falls, road injuries, and interpersonal violence being the leading causes of this condition.</div></div><div><h3>Conclusions</h3><div>While the global burden of SCI is decreasing, the complex distribution across demographics and regions necessitates targeted prevention and treatment strategies to further reduce the burden and improve patient outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102598"},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741625","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":"Fecal microbiota transplantation, a tool to transfer healthy longevity","authors":"Marta G. Novelle ,&nbsp;Beatriz Naranjo-Martínez ,&nbsp;Juan L. López-Cánovas ,&nbsp;Alberto Díaz-Ruiz","doi":"10.1016/j.arr.2024.102585","DOIUrl":"10.1016/j.arr.2024.102585","url":null,"abstract":"<div><div>The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102585"},"PeriodicalIF":12.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-modifying therapies for Alzheimer’s disease: Clinical trial progress and opportunity","authors":"Yujie Zhang ,&nbsp;Jie Chen ,&nbsp;Yanru Li ,&nbsp;Bin Jiao ,&nbsp;Shilin Luo","doi":"10.1016/j.arr.2024.102595","DOIUrl":"10.1016/j.arr.2024.102595","url":null,"abstract":"<div><div>The U.S. Food and Drug Administration (FDA) recently approved lecanemab and donanemab for the treatment of early symptomatic Alzheimer's disease (AD) after their phase III trials reached endpoints. These two anti-amyloid β monoclonal antibodies represent the latest promise of disease-modifying therapy (DMT) for AD, which undoubtedly reignites new hope for DMTs to combat the staggering financial and human costs of AD. However, in addition to these two successful antibodies, there have been enormous efforts to develop DMTs in various aspects to meet the therapeutic requirement of AD. In this review, we delineate the core principles and methodologies of diverse DMTs, covering the advances in clinical trials of drug candidates that either have been discontinued, completed, or are ongoing, as well as brain stimulation and lifestyle interventions. In addition, by overseeing the fate of various candidate molecules, we hope to provide references and ideas for prospective approaches and promising applications of DTMs for AD, particularly in terms of universality and clinical application economics, to optimize efficacy and maximize AD patient benefits in the future.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102595"},"PeriodicalIF":12.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712205","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":"Systematic review of what people know about brain health","authors":"Malwina A. Niechcial ,&nbsp;Shaimaa M. Elhag ,&nbsp;Lauren M. Potter,&nbsp;Adele Dickson,&nbsp;Alan J. Gow","doi":"10.1016/j.arr.2024.102592","DOIUrl":"10.1016/j.arr.2024.102592","url":null,"abstract":"<div><h3>Objectives</h3><div>As we age our cognitive abilities can change. However, the degree of change experienced is influenced by a range of factors. To understand what the public know about risk and protective factors for cognitive ageing, a systematic review was conducted of studies considering what people know about brain health.</div></div><div><h3>Method</h3><div>The search strategy included quantitative and qualitative studies in English, including interviews, focus groups, questionnaires, surveys of beliefs about brain health (including predictions, opinions) in generally healthy adults. PubMed, PsycINFO, Scopus, and Web of Science were used for published peer-reviewed literature; and ProQuest Dissertations and Theses and National Grey Literature Collection, PsycExtra and Google searches for grey literature.</div></div><div><h3>Results</h3><div>From 37,197 records, one hundred and one were included, comprising 71 quantitative (22 grey literature), 27 qualitative (1 grey literature) and 3 mixed-methods (1 grey literature). Studies were grouped into three themes: <em>Concerns about cognitive ageing, Opportunities to promote brain health</em> and <em>Understanding dementia risk reduction and prevention</em>.</div></div><div><h3>Discussion</h3><div>Studies reported varying levels of knowledge of brain health, alongside some suggestions for brain health that were somewhat superficial and not always consistent with scientific consensus. There were differences between groups of participants who exhibited less knowledge of brain health, for example, men, older adults, those with lower education and incomes, and ethnic minorities. This review highlights the need for clear messaging around opportunities to promote brain health, including scientifically-endorsed lifestyle factors and more information on the mechanisms by which they operate.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102592"},"PeriodicalIF":12.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives","authors":"Margrethe A. Olesen,&nbsp;Francisca Villavicencio-Tejo,&nbsp;Víctor Cuevas-Espinoza,&nbsp;Rodrigo A. Quintanilla","doi":"10.1016/j.arr.2024.102594","DOIUrl":"10.1016/j.arr.2024.102594","url":null,"abstract":"<div><div>Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer’s disease (AD) and tauopathies. However, current investigations have implicated tau toxicity in other NDs that affect the central nervous system (CNS), including Parkinson's disease (PD), Huntington's disease (HD), Traumatic brain injury (TBI), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). These diseases are long-term acquired, affecting essential functions such as motor movement, cognition, hearing, and vision. Previous evidence indicated that toxic forms of tau do not have a critical contribution to the genesis or progression of these diseases. However, recent studies have shown that these tau forms contribute to neuronal dysfunction, inflammation, oxidative damage, and mitochondrial impairment events that contribute to the pathogenesis of these NDs. Recent studies have suggested that these neuropathologies could be associated with a prion-like behavior of tau, which induces a pathological dissemination of these toxic protein forms to different brain areas. Moreover, it has been suggested that this toxic propagation of tau from neurons into neighboring cells impairs the function of glial cells, oligodendrocytes, and endothelial cells by affecting metabolic function and mitochondrial health and inducing oxidative damage by tau pathology. Therefore, in this review, we will discuss current evidence demonstrating the critical role of toxic tau forms on NDs not related to AD and how its propagation and induced-bioenergetics failure may contribute to the pathogenic mechanism present in these NDs.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"103 ","pages":"Article 102594"},"PeriodicalIF":12.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694030","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":"Liquid-liquid phase separation in aging: Novel insights in the pathogenesis and therapeutics","authors":"Hua Wang ,&nbsp;Jinxin Tang ,&nbsp;Shuxiang Yan ,&nbsp;Chenbei Li ,&nbsp;Zhaoqi Li ,&nbsp;Zijian Xiong ,&nbsp;Zhihong Li ,&nbsp;Chao Tu","doi":"10.1016/j.arr.2024.102583","DOIUrl":"10.1016/j.arr.2024.102583","url":null,"abstract":"<div><div>The intricate organization of distinct cellular compartments is paramount for the maintenance of normal biological functions and the orchestration of complex biochemical reactions. These compartments, whether membrane-bound organelles or membraneless structures like Cajal bodies and RNA transport granules, play crucial roles in cellular function. Liquid-liquid phase separation (LLPS) serves as a reversible process that elucidates the genesis of membranelles structures through the self-assembly of biomolecules. LLPS has been implicated in a myriad of physiological and pathological processes, encompassing immune response and tumor genesis. But the association between LLPS and aging has not been clearly clarified. A recent advancement in the realm of aging research involves the introduction of a new edition outlining the twelve hallmarks of aging, categorized into three distinct groups. By delving into the role and mechanism of LLPS in the formation of membraneless structures at a molecular level, this review encapsulates an exploration of the interaction between LLPS and these aging hallmarks, aiming to offer novel perspectives of the intricate mechanisms underlying the aging process and deeper insights into aging therapeutics.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102583"},"PeriodicalIF":12.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683652","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 new perspective of Alzheimer's Disease Research: Mechanism and therapeutic strategy of neuronal senescence","authors":"Qianqian Niu ,&nbsp;Danjie Li ,&nbsp;Jiayin Zhang ,&nbsp;Zhengji Piao ,&nbsp;Bo Xu ,&nbsp;Yuting Xi ,&nbsp;Nik Nur Syazni Nik Mohamed Kamal ,&nbsp;Vuanghao Lim ,&nbsp;Peng Li ,&nbsp;Yaling Yin","doi":"10.1016/j.arr.2024.102593","DOIUrl":"10.1016/j.arr.2024.102593","url":null,"abstract":"<div><div>Alzheimer's disease (AD), commonly known as senile dementia, is a neurodegenerative disease with insidious onset and gradually worsening course. The brain is particularly sensitive to senescence, and neuronal senescence is an important risk factor for the occurrence of AD. However, the exact pathogenesis between neuronal senescence and AD has not been fully elucidated so far. Neuronal senescence is characterized by the permanent stagnation of the cell cycle, and the changes in its structure, function, and microenvironment are closely related to the pathogenesis and progression of AD. In recent years, studies such as the Aβ cascade hypothesis and Tau protein phosphorylation have provided new strategies for the therapy of AD, but due to the complexity of the etiology of AD, there are still no effective treatment measures. This article aims to deeply analyze the pathogenesis between AD and neuronal senescence, and sort out various existing therapeutic methods, to provide new ideas and references for the clinical treatment of AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102593"},"PeriodicalIF":12.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683759","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}