Ageing Research Reviews最新文献

{"title":"Sestrin2 is a central regulator of mitochondrial stress responses in disease and aging","authors":"Ivo F. Machado ,&nbsp;Carlos M. Palmeira ,&nbsp;Anabela P. Rolo","doi":"10.1016/j.arr.2025.102762","DOIUrl":"10.1016/j.arr.2025.102762","url":null,"abstract":"<div><div>Mitochondria supply most of the energy for cellular functions and coordinate numerous cellular pathways. Their dynamic nature allows them to adjust to stress and cellular metabolic demands, thus ensuring the preservation of cellular homeostasis. Loss of normal mitochondrial function compromises cell survival and has been implicated in the development of many diseases and in aging. Although exposure to continuous or severe stress has adverse effects on cells, mild mitochondrial stress enhances mitochondrial function and potentially extends health span through mitochondrial adaptive responses. Over the past few decades, sestrin2 (SESN2) has emerged as a pivotal regulator of stress responses. For instance, SESN2 responds to genotoxic, oxidative, and metabolic stress, promoting cellular defense against stress-associated damage. Here, we focus on recent findings that establish SESN2 as an orchestrator of mitochondrial stress adaptation, which is supported by its involvement in the integrated stress response, mitochondrial biogenesis, and mitophagy. Additionally, we discuss the integral role of SESN2 in mediating the health benefits of exercise as well as its impact on skeletal muscle, liver and heart injury, and aging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"109 ","pages":"Article 102762"},"PeriodicalIF":12.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904121","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 context-dependent effect of cellular senescence: From embryogenesis and wound healing to aging","authors":"Rupa Lavarti ,&nbsp;Tatiana Alvarez-Diaz ,&nbsp;Kyarangelie Marti ,&nbsp;Parmita Kar ,&nbsp;Raghavan Pillai Raju","doi":"10.1016/j.arr.2025.102760","DOIUrl":"10.1016/j.arr.2025.102760","url":null,"abstract":"<div><div>Aging is characterized by a steady loss of physiological integrity, leading to impaired function and increased vulnerability to death. Cell senescence is a biological process that progresses with aging and is believed to be a key driver of age-related diseases. Senescence, a hallmark of aging, also demonstrates its beneficial physiological aspects as an anti-cancer, pro-regenerative, homeostatic, and developmental mechanism. A transitory response in which the senescent cells are quickly formed and cleared may promote tissue regeneration and organismal fitness. At the same time, senescence-related secretory phenotypes associated with extended senescence can have devastating effects. The fact that the interaction between senescent cells and their surroundings is very context-dependent may also help to explain this seemingly opposing pleiotropic function. Further, mitochondrial dysfunction is an often-unappreciated hallmark of cellular senescence and figures prominently in multiple feedback loops that induce and maintain the senescent phenotype. This review summarizes the mechanism of cellular senescence and the significance of acute senescence. We concisely introduced the context-dependent role of senescent cells and SASP, aspects of mitochondrial biology altered in the senescent cells, and their impact on the senescent phenotype. Finally, we conclude with recent therapeutic advancements targeting cellular senescence, focusing on acute injuries and age-associated diseases. Collectively, these insights provide a future roadmap for the role of senescence in organismal fitness and life span extension.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"109 ","pages":"Article 102760"},"PeriodicalIF":12.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922231","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":"Ethnicity and frailty: A systematic review of association with prevalence, incidence, trajectories and risks","authors":"Maryam Khan,&nbsp;Barbara I. Nicholl,&nbsp;Peter Hanlon","doi":"10.1016/j.arr.2025.102759","DOIUrl":"10.1016/j.arr.2025.102759","url":null,"abstract":"<div><h3>Background</h3><div>Ethnic variations in frailty are not fully understood. This systematic review examined ethnic differences in the prevalence, incidence and trajectories of frailty; associations between frailty and sociodemographic/lifestyle risk-factors; and health-related outcomes of frailty.</div></div><div><h3>Methods</h3><div>We searched four electronic databases from 2000 to July 2023 using terms for ethnicity and frailty. Inclusion criteria: observational studies assessing frailty in adults ≥ 18 years from community-based settings, including care homes; ethnicity defined by race, country of birth, language, ancestry, or culture. We supplemented searches with manual citation and reference list searches. Outcomes included prevalence, incidence, and transitions of frailty; factors associated with frailty; and health-related outcomes (e.g., mortality). Two reviewers independently screened all articles.</div></div><div><h3>Results</h3><div>We included 82 studies, representing data from 13 countries plus two multi-national samples. Across the included countries, frailty prevalence was higher in minority groups compared to majority groups. Ethnic differences appear sensitive to methods used to measure frailty. Two United States-based studies found that ethnic differences were independent of sociodemographic differences such as income or education. Six studies from the United States or United Kingdom showed that Black and South-Asian people, respectively, had higher frailty incidence or more rapid frailty progression. Two studies showed that frailty was associated with mortality across ethnic groups but with some small differences in magnitude between groups.</div></div><div><h3>Conclusion</h3><div>Ethnic disparities in frailty prevalence persist across community-based settings in different countries and are not fully explained by known inequalities. Addressing these disparities will likely require careful frailty measurement and assessment; confronting structural inequalities; and tailoring interventions to the needs of minoritised populations.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"109 ","pages":"Article 102759"},"PeriodicalIF":12.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900038","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":"Lipid droplets: Emerging therapeutic targets for age-related metabolic diseases","authors":"Zheying Ma ,&nbsp;Shou Pan ,&nbsp;Yaming Yang ,&nbsp;Huiqian Ren ,&nbsp;Sikun Yin ,&nbsp;Qianyu Chen ,&nbsp;Zhenxian An ,&nbsp;Xiaoqin Zhao ,&nbsp;Zujie Xu","doi":"10.1016/j.arr.2025.102758","DOIUrl":"10.1016/j.arr.2025.102758","url":null,"abstract":"<div><div>Lipids metabolism is crucial in regulating aging and metabolic diseases. Lipid droplets (LDs) are dynamic, complex organelles responsible for the storage and release of neutral lipids, essential for maintaining lipid homeostasis and energy metabolism. Aging accelerates the accumulation of LDs, functional deterioration, and metabolic disorders, thereby inducing age-related metabolic diseases (ARMDs). This review examines published datasets on the association between LDs and ARMDs, focusing on the structure and function of LDs, their interactions with other organelles, and associated proteins. Furthermore, we explore the potential mechanisms by which LDs mediate the onset of ARMDs, including Alzheimer’s disease (AD), sarcopenia, metabolic cardiomyopathy, non-alcoholic fatty liver disease (NAFLD), and cancer. Lastly, we discuss intervention strategies aimed at targeting LDs to improve outcomes in ARMDs, including exercise, dietary, and pharmacological interventions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102758"},"PeriodicalIF":12.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886786","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":"Perineuronal nets: Role in normal brain physiology and aging, and pathology of various diseases","authors":"Kaiqi Zhu ,&nbsp;Yifei Fu ,&nbsp;Yinfei Zhao ,&nbsp;Bing Niu ,&nbsp;Han Lu","doi":"10.1016/j.arr.2025.102756","DOIUrl":"10.1016/j.arr.2025.102756","url":null,"abstract":"<div><div>Perineuronal nets (PNNs) are a specialized extracellular matrix in the central nervous system. They are widely distributed in the brain, with distribution patterns varying by brain region. Their unique structure and composition allow them to play an important role in a range of physiological and pathological activities. In this article, we review the composition and structure of PNNs across different life stages, and provide a detailed analysis and comparison of the region-specific distribution patterns of PNNs in different brain areas. We also discuss the specific mechanisms by which PNNs are involved in plasticity, memory, and neuroprotection. Furthermore, we describe the abnormal changes in PNNs in aging and various brain diseases, such as Alzheimer's disease, Parkinson's disease, drug addiction, and schizophrenia. Finally, we review emerging and established therapeutic strategies targeting PNNs to modulate brain function and address neurological disorders from three perspectives: gene therapy, nanotechnology, and biomaterials. This review summarizes the physiological roles of PNNs at different stages of life and the mechanisms by which PNNs abnormalities contribute to various brain diseases, providing insights for potential therapeutic approaches.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102756"},"PeriodicalIF":12.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851475","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 redundant landscape of meta-analyses: Evaluating exercise interventions for older adults with cognitive impairment","authors":"Julie D. Ries ,&nbsp;Claudia De Santis ,&nbsp;Mahederemariam Bayleyegn Dagne ,&nbsp;Kaoutar Ouabicha ,&nbsp;Pallavi Sood ,&nbsp;Patricia C. Heyn","doi":"10.1016/j.arr.2025.102754","DOIUrl":"10.1016/j.arr.2025.102754","url":null,"abstract":"<div><h3>Background</h3><div>Exercise to benefit cognition in older adults with cognitive impairment is well-studied. A recent proliferation of synthesis studies might be a positive contribution to the science; however, redundancy in research can be wasteful and detrimental to drawing confident conclusions about the evidence. This synthesis-based method study was designed to analyze: 1) the frequency and growth patterns of meta-analyses (MAs) and randomized controlled trials (RCTs) on this topic; and 2) the redundancy rate of the RCT studies included in MAs.</div></div><div><h3>Methods</h3><div>This study was borne of a living systematic review, following standard synthesis methodology (PROSPERO registration, librarian-assisted search algorithms developed for multiple databases, searches updated regularly with most recent search in 2025). Frequency counts determined the number of RCTs and how many times they were included across the MAs.</div></div><div><h3>Results</h3><div>Forty MAs were identified and included in the synthesis representing a total of 728 RCT studies. After reviewing RCT duplicates, 276 (37.9%) unique RCT studies comprised this body of evidence. Among these, 153 RCTs were cited in only one MA and 123 were cited in 2-19 different MAs. Thus, 452 (62.1%) of all RCTs used across the 40 MAs were redundant (i.e., represented in more than one MA).</div></div><div><h3>Conclusions</h3><div>This study found substantial redundancy in the RCTs used in MAs evaluating the cognitive impact of exercise for older adults with cognitive impairment. Replication is common practice in research but reliance on the same RCTs in multiple MAs creates an illusion of robustness when, in fact, the strength and diversity of the evidence may be more limited. Research redundancy is wasteful and may actually stagnate advancement of this science.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102754"},"PeriodicalIF":12.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864881","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":"Past, present, and future of serotonin-targeting therapeutics for Alzheimer’s disease: Perspectives from DNA methylation","authors":"Yanzhi Liu ,&nbsp;Luca Aquili ,&nbsp;Kah Hui Wong ,&nbsp;Zhiliang Lu ,&nbsp;Lee Wei Lim","doi":"10.1016/j.arr.2025.102755","DOIUrl":"10.1016/j.arr.2025.102755","url":null,"abstract":"<div><div>With population aging, Alzheimer’s disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood disturbances. This review discusses the critical involvement of the brain 5-HT system in aging and AD. Existing findings on the changes in projection fiber innervation and receptor/transporter expression in AD are reviewed. Preclinical and clinical progress on the development of 5-HT-modulating drugs for AD and the obstacles faced by these development efforts are discussed. Epigenetic control of the brain 5-HT system and the potential of modulating 5-HT transmission via DNA methylation are also examined.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102755"},"PeriodicalIF":12.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864882","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":"Transformative advances in modeling brain aging and longevity: Success, challenges and future directions","authors":"Varsha Pai ,&nbsp;Bhisham Narayan Singh ,&nbsp;Abhishek Kumar Singh","doi":"10.1016/j.arr.2025.102753","DOIUrl":"10.1016/j.arr.2025.102753","url":null,"abstract":"<div><div>Research on brain aging is crucial for understanding age-related neurodegenerative disorders and developing several therapeutic interventions. Numerous models ranging from two-dimensional (2D) cell-based, invertebrate, vertebrate, and sophisticated three-dimensional (3D) models have been used to understand the process of brain aging. Invertebrate models are ideal for researching conserved aging processes because of their simplicity, short lifespans, and genetic tractability. Moreover, vertebrate models, including zebrafish and rodents, exhibit more complex nervous systems and behaviors, enabling the exploration of age-related neurodegeneration and cognitive decline. 2D cell culture models derived from primary cells or immortalized cell lines are widely used for mechanistic studies at the cellular level but lack the physiological complexity of brain tissue. Recent advancements have shifted focus to 3D models, which better recapitulate the brain’s microenvironment. Organoids derived from induced pluripotent stem cells mimic human brain architecture and enable the study of cell-cell interactions and aging in a human-specific context. Brain-on-a-chip systems integrate microfluidics and 3D cultures to model blood-brain barrier dynamics and neuronal networks. Additionally, scaffold-based 3D cultures and spheroids provide intermediate complexity, allowing researchers to study extracellular matrix interactions and age-related changes in neuronal function. These 3D models bridge the gap between traditional 2D cultures and animal-based <em>in vivo</em> studies, offering unprecedented insights into brain aging mechanisms. By combining these diverse models, researchers can unravel the multifaceted processes of brain aging and accelerate the development of targeted therapies for age-related neurodegenerative disorders.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102753"},"PeriodicalIF":12.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833247","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 the three major intestinal barriers in ulcerative colitis in the elderly","authors":"Min Fu ,&nbsp;Qi-Wen Wang ,&nbsp;Ya-Ru Liu ,&nbsp;Shu-Jie Chen","doi":"10.1016/j.arr.2025.102752","DOIUrl":"10.1016/j.arr.2025.102752","url":null,"abstract":"<div><div>With the unprecedented pace of global population aging, there has been a parallel epidemiological shift marked by increasing incidence rates of ulcerative colitis (UC) in geriatric populations, imposing a substantial disease burden on healthcare systems globally. The etiopathogenesis of UC in the elderly remains poorly delineated, while current therapeutic strategies require further optimization to accommodate the unique pathophysiological characteristics of elderly patients. This review systematically elucidates the three barrier dysfunction - encompassing the gut microbiota ecosystem, mucosal epithelial integrity, and immunoregulatory network - that collectively drives UC pathogenesis during biological senescence. We emphasize the therapeutic potential of barrier-targeted interventions, particularly highlighting emerging modalities including fecal microbiota transplantation, intestinal organoid regeneration techniques, mesenchymal stem cell-mediated immunomodulation, and precision-engineered Chimeric Antigen Receptor T-cell therapies. Through this multidimensional analysis, we propose a paradigm-shifting approach to UC management in the elderly, advocating for the development of tailored and evidence-based therapeutic interventions that address the complex interplay between age-related biological changes and intestinal barrier homeostasis in elderly patients.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102752"},"PeriodicalIF":12.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817733","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":"Reducing Alzheimer’s disease risk with SGLT2 inhibitors: From glycemic control to neuroprotection","authors":"Mehdi Alami ,&nbsp;Mojgan Morvaridzadeh ,&nbsp;Abdellatif El Khayari ,&nbsp;Kaoutar Boumezough ,&nbsp;Rachid El Fatimy ,&nbsp;Abdelouahed Khalil ,&nbsp;Tamas Fulop ,&nbsp;Hicham Berrougui","doi":"10.1016/j.arr.2025.102751","DOIUrl":"10.1016/j.arr.2025.102751","url":null,"abstract":"<div><div>Recent research has established a strong link between metabolic abnormalities and an increased risk of dementia. In parallel, there is growing epidemiological evidence supporting the neuroprotective effects of antidiabetic medications against cognitive impairments. Among these, sodium-glucose co-transporter (SGLT2) inhibitors have emerged as pharmacological candidates with promising potential in alleviating the burden of age-related diseases, particularly neurodegenerative diseases (NDD). SGLT2 inhibitor therapies are FDA-approved medications routinely prescribed to manage diabetes. This novel class was initially developed to address cardiovascular disorders and to reduce the risk of hypoglycemia associated with insulin-secretagogue agents. It subsequently attracted growing interest for its beneficial effects on central nervous system (CNS) disorders. However, the molecular mechanisms through which these glucose-lowering therapies mitigate cognitive decline and limit the progression of certain brain degenerative diseases remain largely unexplored. Consequently, the neuroscientific community needs further studies that gather, analyze, and critically discuss the available mechanistic evidence regarding the neuroprotective effects of SGLT2 inhibitors. This review aims to critically examine the most relevant published findings, both <em>in vitro</em> and <em>in vivo</em>, as well as human studies evaluating the impact of SGLT2 inhibitors exposure on Alzheimer’s disease (AD). It seeks to integrate the current understanding of their beneficial effects at the molecular level and their role in addressing the pathophysiology and neuropathology of AD. These insights will help extend our knowledge of how SGLT2 inhibitor therapies are associated with reduced risk of dementia and thus shed light on the link between diabetes and AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"108 ","pages":"Article 102751"},"PeriodicalIF":12.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808151","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}