Pub Date : 2025-12-08DOI: 10.1016/j.arr.2025.102988
Eva Kočar , Robert Šket , Ana Halužan Vasle , Gorazd Avguštin , Evgen Benedik , Barbara Koroušić Seljak , Pavle Simić , Antonio Martinko , Shawnda A. Morrison , Maroje Sorić , Mihaela Skrt , Tomaž Polak , Tine Tesovnik , Barbara Jenko Bizjan , Jernej Kovač , Tadej Battelino , Damjana Rozman , Nataša Poklar Ulrih , Bojana Bogovič Matijašić , Gregor Jurak , Tadeja Režen
Biological ageing is a systemic, multifactorial process driven by progressive molecular and cellular alterations whose complexity necessitates systems-level approaches. Advances in high-throughput omics technologies now allow simultaneous quantification of millions of biomolecules from a single specimen, enabling longitudinal, integrative profiling across multiple molecular layers. This review synthesizes recent progress in applying genomics, epigenomics, metabolomics and microbiomics to ageing research, highlighting their contributions to biomarker discovery, mechanistic insight, and translational opportunities. Genomic studies reveal genetic variants that promote extreme longevity, while epigenetic clocks provide robust predictors of biological age. The blood proteome can be used to calculate proteome-based scores and evaluate temporal changes in ageing trajectories in an organ- and sex-specific manner. Metabolomic signatures identify key metabolites reflecting ageing trajectories, and microbiome research demonstrates that gut microbial composition mirrors and modulates biological ageing, with microbiome clocks emerging. The omics approaches have further elucidated the impact of exercise and diet providing evidence that interventions can reduce biological age. The integration of multi-omics with clinical and lifestyle data, powered by machine learning and artificial intelligence, is paving the way for a holistic definition of biological age and the development of personalized healthy ageing strategies. This review highlights how the omics technologies and computational modelling are transforming ageing biology into strategies for personalized healthy ageing.
{"title":"Measuring biological age: Insights from omics studies","authors":"Eva Kočar , Robert Šket , Ana Halužan Vasle , Gorazd Avguštin , Evgen Benedik , Barbara Koroušić Seljak , Pavle Simić , Antonio Martinko , Shawnda A. Morrison , Maroje Sorić , Mihaela Skrt , Tomaž Polak , Tine Tesovnik , Barbara Jenko Bizjan , Jernej Kovač , Tadej Battelino , Damjana Rozman , Nataša Poklar Ulrih , Bojana Bogovič Matijašić , Gregor Jurak , Tadeja Režen","doi":"10.1016/j.arr.2025.102988","DOIUrl":"10.1016/j.arr.2025.102988","url":null,"abstract":"<div><div>Biological ageing is a systemic, multifactorial process driven by progressive molecular and cellular alterations whose complexity necessitates systems-level approaches. Advances in high-throughput omics technologies now allow simultaneous quantification of millions of biomolecules from a single specimen, enabling longitudinal, integrative profiling across multiple molecular layers. This review synthesizes recent progress in applying genomics, epigenomics, metabolomics and microbiomics to ageing research, highlighting their contributions to biomarker discovery, mechanistic insight, and translational opportunities. Genomic studies reveal genetic variants that promote extreme longevity, while epigenetic clocks provide robust predictors of biological age. The blood proteome can be used to calculate proteome-based scores and evaluate temporal changes in ageing trajectories in an organ- and sex-specific manner. Metabolomic signatures identify key metabolites reflecting ageing trajectories, and microbiome research demonstrates that gut microbial composition mirrors and modulates biological ageing, with microbiome clocks emerging. The omics approaches have further elucidated the impact of exercise and diet providing evidence that interventions can reduce biological age. The integration of multi-omics with clinical and lifestyle data, powered by machine learning and artificial intelligence, is paving the way for a holistic definition of biological age and the development of personalized healthy ageing strategies. This review highlights how the omics technologies and computational modelling are transforming ageing biology into strategies for personalized healthy ageing.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102988"},"PeriodicalIF":12.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727616","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}
Pub Date : 2025-12-08DOI: 10.1016/j.arr.2025.102987
Shiliang Hu , Zhen Yang , Kaiming Bao , Wenlong Hou , Yuanyuan Qin , Chu Wu , QingMei Wang , Xun Luo , Li Luo
Background
Dysregulation of mitochondrial dynamics, including fusion/fission, transport, mitophagy and biogenesis, plays a crucial role in neurodegenerative diseases. However, a systematic quantitative mapping of the knowledge structure (i.e., key research themes, foundational references, and citation/collaboration clusters) and evolving research trends (i.e., research hotspots over time) in this research field is lacking.
Methods
Empirical and review article on mitochondrial dynamics in neurodegenerative diseases, which published in English from 2005 to 2025, were retrieved from the Web of Science Core Collection and Scopus. BibliometriX, VOSviewer, and CiteSpace were applied to perform the bibliometric analysis and science mapping. Scientific performance analyses, collaborative networks of authors/institutions/countries, reference co-citation networks, keyword bursts analysis were conducted.
Results
A total of 834 documents were included, revealing a rapid growth in scientific productivity from 2005 to 2025. The United States, China, and Germany were the most productive countries, with institutions such as Case Western Reserve University and Texas Tech University serving as major hubs. Co-citation and keyword burst analyses reveal a distinct temporal shift: from foundational studies of fusion/fission machinery and oxidative stress toward an integrated Mitochondrial Quality Control paradigm encompassing mitophagy, dynamics, and biogenesis. Key emerging hotspots include mitochondrial biogenesis, mitochondrial transport, and quality control mechanisms. Translational frontiers prioritize enhancing PINK1/Parkin-mediated mitophagy, inhibiting Drp1-driven excessive fission, and activating PGC-1α-dependent biogenesis.
Conclusion
This bibliometric study maps the intellectual structure and evolutionary trajectory of mitochondrial dynamics research in neurodegenerative diseases. It documents a field-wide paradigm shift toward a translational agenda centered on the MQC framework. Furthermore, the findings highlight the necessity of integrating pharmacological interventions with lifestyle modifications and precision medicine approaches to overcome translational barriers and develop effective disease-modifying strategies.
{"title":"Mitochondrial dynamics in neurodegenerative diseases: Research hotspots and trends from 2005 to 2025","authors":"Shiliang Hu , Zhen Yang , Kaiming Bao , Wenlong Hou , Yuanyuan Qin , Chu Wu , QingMei Wang , Xun Luo , Li Luo","doi":"10.1016/j.arr.2025.102987","DOIUrl":"10.1016/j.arr.2025.102987","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulation of mitochondrial dynamics, including fusion/fission, transport, mitophagy and biogenesis, plays a crucial role in neurodegenerative diseases. However, a systematic quantitative mapping of the knowledge structure (i.e., key research themes, foundational references, and citation/collaboration clusters) and evolving research trends (i.e., research hotspots over time) in this research field is lacking.</div></div><div><h3>Methods</h3><div>Empirical and review article on mitochondrial dynamics in neurodegenerative diseases, which published in English from 2005 to 2025, were retrieved from the Web of Science Core Collection and Scopus. BibliometriX, VOSviewer, and CiteSpace were applied to perform the bibliometric analysis and science mapping. Scientific performance analyses, collaborative networks of authors/institutions/countries, reference co-citation networks, keyword bursts analysis were conducted.</div></div><div><h3>Results</h3><div>A total of 834 documents were included, revealing a rapid growth in scientific productivity from 2005 to 2025. The United States, China, and Germany were the most productive countries, with institutions such as Case Western Reserve University and Texas Tech University serving as major hubs. Co-citation and keyword burst analyses reveal a distinct temporal shift: from foundational studies of fusion/fission machinery and oxidative stress toward an integrated Mitochondrial Quality Control paradigm encompassing mitophagy, dynamics, and biogenesis. Key emerging hotspots include mitochondrial biogenesis, mitochondrial transport, and quality control mechanisms. Translational frontiers prioritize enhancing PINK1/Parkin-mediated mitophagy, inhibiting Drp1-driven excessive fission, and activating PGC-1α-dependent biogenesis.</div></div><div><h3>Conclusion</h3><div>This bibliometric study maps the intellectual structure and evolutionary trajectory of mitochondrial dynamics research in neurodegenerative diseases. It documents a field-wide paradigm shift toward a translational agenda centered on the MQC framework. Furthermore, the findings highlight the necessity of integrating pharmacological interventions with lifestyle modifications and precision medicine approaches to overcome translational barriers and develop effective disease-modifying strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102987"},"PeriodicalIF":12.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727640","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}
Pub Date : 2025-12-08DOI: 10.1016/j.arr.2025.102989
Kamlesh Kumar Pandey , Abhay Mishra , Ram Milan
Alzheimer's disease (AD) is one of the brain's neurodegenerative diseases. It is distinguished by a progressive mental, social, and behavioral deterioration. It affects the person's capacity, thinking, attention, reasoning, social behavior and functionality to achieve independence. The classical diagnosis process of AD consists of variety of neuroimaging scan approaches such as computerized tomography, magnetic resonance imaging and positron emission tomography. Classical cerebrospinal fluid biomarkers such as amyloid-β₄₂, total tau, and phosphorylated tau are used in conjunction with neuroimaging to diagnose Alzheimer’s disease. Biomarkers are used inside of neuro scan images to measure the brain's structure and functions such as brain cortical thinning, brain atrophy and glucose metabolism. The Classical cerebrospinal fluid biomarkers such as amyloid-β₄₂, total tau, and phosphorylated tau are used in conjunction with neuroimaging to diagnose Alzheimer’s disease. The classical diagnosis processes identified Alzheimer's disease through the manual manipulation of biomarkers in neuroimages. Therefore, the classical AD diagnosis processes suffer from time, cost and accuracy-related challenges. Machine learning and deep learning are the rising predictive modeling techniques that automatically diagnose AD with high accuracy and minimum time. The predictive modeling avoids manual manipulation of biomarkers and combines the processes of neuro scans and biomarkers. The integration of artificial intelligence with AD diagnoses addresses prevailing technological challenges in problem-solving and decision support. This study details and discusses the predictive modeling process and principal components with respect to the AD diagnosis process. The predictive model emphasizes the significance of diverse machine learning and deep learning algorithms. The predictive model utilized neuroimaging techniques, biomarker identification, features and data management, preprocessing, ML and DL algorithms, data sets, and performance matrices. This study also analyzes various classical predictive models and determines the performance level of the classifier, preprocessing steps, dataset, and validation metrics.
{"title":"Predictive modeling approaches for Alzheimer's disease diagnosis through neuroimaging techniques","authors":"Kamlesh Kumar Pandey , Abhay Mishra , Ram Milan","doi":"10.1016/j.arr.2025.102989","DOIUrl":"10.1016/j.arr.2025.102989","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is one of the brain's neurodegenerative diseases. It is distinguished by a progressive mental, social, and behavioral deterioration. It affects the person's capacity, thinking, attention, reasoning, social behavior and functionality to achieve independence. The classical diagnosis process of AD consists of variety of neuroimaging scan approaches such as computerized tomography, magnetic resonance imaging and positron emission tomography. Classical cerebrospinal fluid biomarkers such as amyloid-β₄₂, total tau, and phosphorylated tau are used in conjunction with neuroimaging to diagnose Alzheimer’s disease. Biomarkers are used inside of neuro scan images to measure the brain's structure and functions such as brain cortical thinning, brain atrophy and glucose metabolism. The Classical cerebrospinal fluid biomarkers such as amyloid-β₄₂, total tau, and phosphorylated tau are used in conjunction with neuroimaging to diagnose Alzheimer’s disease. The classical diagnosis processes identified Alzheimer's disease through the manual manipulation of biomarkers in neuroimages. Therefore, the classical AD diagnosis processes suffer from time, cost and accuracy-related challenges. Machine learning and deep learning are the rising predictive modeling techniques that automatically diagnose AD with high accuracy and minimum time. The predictive modeling avoids manual manipulation of biomarkers and combines the processes of neuro scans and biomarkers. The integration of artificial intelligence with AD diagnoses addresses prevailing technological challenges in problem-solving and decision support. This study details and discusses the predictive modeling process and principal components with respect to the AD diagnosis process. The predictive model emphasizes the significance of diverse machine learning and deep learning algorithms. The predictive model utilized neuroimaging techniques, biomarker identification, features and data management, preprocessing, ML and DL algorithms, data sets, and performance matrices. This study also analyzes various classical predictive models and determines the performance level of the classifier, preprocessing steps, dataset, and validation metrics.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102989"},"PeriodicalIF":12.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727652","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}
Pub Date : 2025-12-06DOI: 10.1016/j.arr.2025.102986
Danrui Zhao , Junting Wang , Fengji Zhang , Qing Wang , Mengqing Zang , Haijing Niu , Zhiqian Tong
The glymphatic system was initially considered as a perivascular channel, responsible for the clearance of substances within the brain. With the deepening comprehension of the functions of the extracellular space (ECS) and the discovery of meningeal lymphatic vessels and subarachnoid lymphatic-like membrane, it is proposed that the glymphatic system should be a complex system encompassing the perivascular space, ECS, and lymphatic-like structures, and it plays crucial roles in the delivery of substances, waste clearance, and neuroimmune functions within the brain. Recent studies have revealed that brain ECS essentially regulates these fundamental functions, including sleep, memory, and sensory processing. Here, in this review, we delineate advances in the roles of glymphatic system in structure, functions, ageing and brain diseases. The imaging technologies have facilitated a more nuanced understanding of the glymphatic system's architecture, particularly the pericellular space. The compartmentalized system, characterized by myelin sheath separation, serves as the conduit for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a predominant role in modulating the ISF within the deep brain region. Furthermore, we discuss the pathophysiological implications of excessive formaldehyde (FA) accumulation in the aging brain. Especially, ageing-associated FA can cross-link Aβ, tau, α-synuclein, hemoglobin and extracellular matrix in the ECS and/or endochylema, which leads to the disorder of ISF-CSF exchanges and encephalopathy onset, such as: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, gliomas and sleep disorders. Hence, glymphatic system including ECS may be a promising therapeutic target for brain diseases.
{"title":"Cerebral glymphatic system: Structure, regulation, ageing, and mechanisms of encephalopathy","authors":"Danrui Zhao , Junting Wang , Fengji Zhang , Qing Wang , Mengqing Zang , Haijing Niu , Zhiqian Tong","doi":"10.1016/j.arr.2025.102986","DOIUrl":"10.1016/j.arr.2025.102986","url":null,"abstract":"<div><div>The glymphatic system was initially considered as a perivascular channel, responsible for the clearance of substances within the brain. With the deepening comprehension of the functions of the extracellular space (ECS) and the discovery of meningeal lymphatic vessels and subarachnoid lymphatic-like membrane, it is proposed that the glymphatic system should be a complex system encompassing the perivascular space, ECS, and lymphatic-like structures, and it plays crucial roles in the delivery of substances, waste clearance, and neuroimmune functions within the brain. Recent studies have revealed that brain ECS essentially regulates these fundamental functions, including sleep, memory, and sensory processing. Here, in this review, we delineate advances in the roles of glymphatic system in structure, functions, ageing and brain diseases. The imaging technologies have facilitated a more nuanced understanding of the glymphatic system's architecture, particularly the pericellular space. The compartmentalized system, characterized by myelin sheath separation, serves as the conduit for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a predominant role in modulating the ISF within the deep brain region. Furthermore, we discuss the pathophysiological implications of excessive formaldehyde (FA) accumulation in the aging brain. Especially, ageing-associated FA can cross-link Aβ, tau, α-synuclein, hemoglobin and extracellular matrix in the ECS and/or endochylema, which leads to the disorder of ISF-CSF exchanges and encephalopathy onset, such as: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, gliomas and sleep disorders. Hence, glymphatic system including ECS may be a promising therapeutic target for brain diseases.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102986"},"PeriodicalIF":12.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710350","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}
Pub Date : 2025-12-04DOI: 10.1016/j.arr.2025.102981
Grace H. Shim , Edward C.Y. Lau , Andrew L.H. Huynh , Christine Y. Lu , Edwin C.K. Tan
Background
Lecanemab and donanemab are the first anti-amyloid monoclonal antibodies (mAbs) clinically available as disease-modifying therapies for Alzheimer’s disease (AD). However, it remains unclear whether their treatment effects differ across demographic, clinical, or genetic subgroups.
Objective
This systematic review aimed to explore how patient characteristics modify the efficacy, safety and humanistic outcomes of anti-amyloid mAbs lecanemab and donanemab in patients with early AD.
Methods
A systematic search of MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library was conducted from database inception to July 30th, 2025, using a combination of keywords and Medical Subject Heading terms relating to lecanemab and donanemab. Meta-analyses were conducted for safety outcomes where sufficient data was available.
Results
Sixteen studies representing six randomised clinical trials (total N = 5633) were included. Both lecanemab and donanemab showed the greatest slowing of cognitive decline in White/Caucasian patients and apolipoprotein E4 (ApoE4) non-carriers. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) and microhemorrhages (ARIA-H) were more prevalent in ApoE4 carriers. The risk of ARIA-E was 2.19 times higher (95 %CI:1.91–2.50) and ARIA-H was 3.45 times higher (95 %CI:1.35–8.72) in ApoE4 carriers versus non-carriers. Statistically significant improvements in health-related quality of life were observed with lecanemab in ApoE4 heterozygous participants and in those aged 65–74 years.
Conclusions
The efficacy and safety of anti-amyloid mAbs in AD may differ based on patients’ demographic and genetic factors. These findings highlight the potential for personalised treatment strategies and inform national drug policies. Further research is needed to evaluate long-term outcomes and address under-studied patient populations.
Summary
The efficacy and safety of lecanemab and donanemab varied across patient subgroups, including age, sex, race/ethnicity and genetic factors such as ApoE4 genotype status. The risk of ARIA was higher in ApoE4 carriers, particularly the homozygous.
{"title":"Influence of patient characteristics on efficacy and safety of anti-amyloid monoclonal antibodies in Alzheimer’s disease: A systematic review and meta-analysis","authors":"Grace H. Shim , Edward C.Y. Lau , Andrew L.H. Huynh , Christine Y. Lu , Edwin C.K. Tan","doi":"10.1016/j.arr.2025.102981","DOIUrl":"10.1016/j.arr.2025.102981","url":null,"abstract":"<div><h3>Background</h3><div>Lecanemab and donanemab are the first anti-amyloid monoclonal antibodies (mAbs) clinically available as disease-modifying therapies for Alzheimer’s disease (AD). However, it remains unclear whether their treatment effects differ across demographic, clinical, or genetic subgroups.</div></div><div><h3>Objective</h3><div>This systematic review aimed to explore how patient characteristics modify the efficacy, safety and humanistic outcomes of anti-amyloid mAbs lecanemab and donanemab in patients with early AD.</div></div><div><h3>Methods</h3><div>A systematic search of MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library was conducted from database inception to July 30th, 2025, using a combination of keywords and Medical Subject Heading terms relating to lecanemab and donanemab. Meta-analyses were conducted for safety outcomes where sufficient data was available.</div></div><div><h3>Results</h3><div>Sixteen studies representing six randomised clinical trials (total N = 5633) were included. Both lecanemab and donanemab showed the greatest slowing of cognitive decline in White/Caucasian patients and apolipoprotein E4 (ApoE4) non-carriers. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) and microhemorrhages (ARIA-H) were more prevalent in ApoE4 carriers. The risk of ARIA-E was 2.19 times higher (95 %CI:1.91–2.50) and ARIA-H was 3.45 times higher (95 %CI:1.35–8.72) in ApoE4 carriers versus non-carriers. Statistically significant improvements in health-related quality of life were observed with lecanemab in ApoE4 heterozygous participants and in those aged 65–74 years.</div></div><div><h3>Conclusions</h3><div>The efficacy and safety of anti-amyloid mAbs in AD may differ based on patients’ demographic and genetic factors. These findings highlight the potential for personalised treatment strategies and inform national drug policies. Further research is needed to evaluate long-term outcomes and address under-studied patient populations.</div></div><div><h3>Summary</h3><div>The efficacy and safety of lecanemab and donanemab varied across patient subgroups, including age, sex, race/ethnicity and genetic factors such as ApoE4 genotype status. The risk of ARIA was higher in ApoE4 carriers, particularly the homozygous.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102981"},"PeriodicalIF":12.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694412","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}
Pub Date : 2025-12-04DOI: 10.1016/j.arr.2025.102983
Xiaosu Wang , Zhihui Feng , Sa Sun , Jiehao Zhang , Kexin Wang , Yiwen Wang , Yameng Zhao , Bizhu Zhao , Bo Liu , Mengli Sun , Zongming Song , Ye Tao
Aging-related retinal diseases lead to irreversible structural damages and vision loss. These conditions are characterized by cellular senescence, oxidative stress, neural degeneration, and neovascularization. Among these, chronic inflammation is a hallmark of aging, establishing a self-perpetuating vicious cycle that accelerates pathological process and physiological decline. cGAS-STING signaling pathway has been identified as a critical mediator of inflammation across multiple retinal disease contexts, functioning to regulate immune response by detecting the dsDNA resulted from tissue injury. Under pathological circumstances, it exhibits a state of persistent activation, which results in chronic inflammatory reactions in the microenvironment. The disrupted homeostasis is closely linked with the onset and progression of numerous aging-related retinal diseases. Given the strong association between cGAS-STING signaling and these conditions, this pathway may represent a promising therapeutic target for refractory retinopathies. Encouragingly, several inhibitors targeting this pathway have already been developed and yielded remarkable therapeutic outcomes. This review delineates the primary functioning factors and modulatory mechanisms of the cGAS-STING cascade. Furthermore, it discusses the specific role of cGAS-STING pathway in pathological process of age-related retinopathy and summarize the key inhibitors of the cGAS-STING pathway, highlighting their therapeutic potentials for age-related retinopathy. These findings will deepen the understanding of the crosstalk between cGAS-STING signaling and retinal aging, thus offering valuable insights for the future translation of laboratory findings into clinical interventions.
{"title":"cGAS-STING-driven inflammaging cascade in aging-related retinal diseases: From pathological mechanism to therapeutic potentials","authors":"Xiaosu Wang , Zhihui Feng , Sa Sun , Jiehao Zhang , Kexin Wang , Yiwen Wang , Yameng Zhao , Bizhu Zhao , Bo Liu , Mengli Sun , Zongming Song , Ye Tao","doi":"10.1016/j.arr.2025.102983","DOIUrl":"10.1016/j.arr.2025.102983","url":null,"abstract":"<div><div>Aging-related retinal diseases lead to irreversible structural damages and vision loss. These conditions are characterized by cellular senescence, oxidative stress, neural degeneration, and neovascularization. Among these, chronic inflammation is a hallmark of aging, establishing a self-perpetuating vicious cycle that accelerates pathological process and physiological decline. cGAS-STING signaling pathway has been identified as a critical mediator of inflammation across multiple retinal disease contexts, functioning to regulate immune response by detecting the dsDNA resulted from tissue injury. Under pathological circumstances, it exhibits a state of persistent activation, which results in chronic inflammatory reactions in the microenvironment. The disrupted homeostasis is closely linked with the onset and progression of numerous aging-related retinal diseases. Given the strong association between cGAS-STING signaling and these conditions, this pathway may represent a promising therapeutic target for refractory retinopathies. Encouragingly, several inhibitors targeting this pathway have already been developed and yielded remarkable therapeutic outcomes. This review delineates the primary functioning factors and modulatory mechanisms of the cGAS-STING cascade. Furthermore, it discusses the specific role of cGAS-STING pathway in pathological process of age-related retinopathy and summarize the key inhibitors of the cGAS-STING pathway, highlighting their therapeutic potentials for age-related retinopathy. These findings will deepen the understanding of the crosstalk between cGAS-STING signaling and retinal aging, thus offering valuable insights for the future translation of laboratory findings into clinical interventions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102983"},"PeriodicalIF":12.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688929","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}
Pub Date : 2025-12-03DOI: 10.1016/j.arr.2025.102974
Rocco Sheldon , Andrew Gan , Jennifer Tasong , Audrey Yap , Moiz Ahmad , Paulo Roberto Hernandes Júnior , Kailash Viswanathan , Naga Sai Manas Setti , Olivia Jarman , Shuayb Hoque-Uddin , Tanisha Banerjee , James E. Turner , Simon W. Jones , Amanda Veiga Sardeli
Background
The relationship between metabolic and inflammatory adaptations with exercise training is poorly quantified. We employed a novel meta-analytical approach to provide an evidence-based framework to guide exercise prescription for health in older adults.
Methods
This systematic review (PROSPERO: CRD42025630662) identified controlled exercise training interventions in older adults. We meta-analysed 146 studies assessing body mass, BMI, fat mass, muscle mass, circulating CRP, IL-6, TNF-α, adiponectin, leptin, IGF-1, IL-1β, fasting glucose, insulin, glycated haemoglobin, HOMA-IR, TG, total cholesterol, LDL-C, HDL-C, and VO2 max. Our novel analytical approach divided studies into “improved” or “not improved” for each variable based on the significant direction of their standardised mean difference (95 % CI), followed by a cross-over subgroup analysis.
Results
Meta-analyses showed that exercise training improved all outcomes, except for IL-1β. Aerobic training showed the greatest overall benefits—except for IGF-1—while resistance training improved most markers but did not reduce body mass and IL-6. A frequency of at least 3 sessions per week was necessary to reduce body mass, insulin, HOMA-IR, triglycerides, total cholesterol, IL-6, TNF-α, leptin, and to increase adiponectin and IGF-1. Shorter interventions (< 12 weeks) led to greater increases in adiponectin and IGF-1 and stronger reductions in TNF-α and IL-1β, suggesting a transient response. Women, unhealthy individuals, and those who were overweight or obese exhibited greater improvements than their counterparts. Anti-inflammatory effects were more pronounced when accompanied by decreases in body mass, fat mass, and improved glucose and lipid metabolism, but was not dependent on those changes.
Conclusion
Aerobic training is the most effective intervention, followed by resistance training, and at least 3 sessions per week (or twice a week for more than 24 weeks) are needed for metabolic and anti-inflammatory adaptations. This compendium provides a reference point for personalised exercise plans for treatment and prevention of chronic diseases—especially for older adults with metabolic conditions.
{"title":"Exercise-induced inflammatory and metabolic adaptations in ageing: A meta-analytic compendium","authors":"Rocco Sheldon , Andrew Gan , Jennifer Tasong , Audrey Yap , Moiz Ahmad , Paulo Roberto Hernandes Júnior , Kailash Viswanathan , Naga Sai Manas Setti , Olivia Jarman , Shuayb Hoque-Uddin , Tanisha Banerjee , James E. Turner , Simon W. Jones , Amanda Veiga Sardeli","doi":"10.1016/j.arr.2025.102974","DOIUrl":"10.1016/j.arr.2025.102974","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between metabolic and inflammatory adaptations with exercise training is poorly quantified. We employed a novel meta-analytical approach to provide an evidence-based framework to guide exercise prescription for health in older adults.</div></div><div><h3>Methods</h3><div>This systematic review (PROSPERO: CRD42025630662) identified controlled exercise training interventions in older adults. We meta-analysed 146 studies assessing body mass, BMI, fat mass, muscle mass, circulating CRP, IL-6, TNF-α, adiponectin, leptin, IGF-1, IL-1β, fasting glucose, insulin, glycated haemoglobin, HOMA-IR, TG, total cholesterol, LDL-C, HDL-C, and VO<sub>2</sub> max. Our novel analytical approach divided studies into “improved” or “not improved” for each variable based on the significant direction of their standardised mean difference (95 % CI), followed by a cross-over subgroup analysis.</div></div><div><h3>Results</h3><div>Meta-analyses showed that exercise training improved all outcomes, except for IL-1β. Aerobic training showed the greatest overall benefits—except for IGF-1—while resistance training improved most markers but did not reduce body mass and IL-6. A frequency of at least 3 sessions per week was necessary to reduce body mass, insulin, HOMA-IR, triglycerides, total cholesterol, IL-6, TNF-α, leptin, and to increase adiponectin and IGF-1. Shorter interventions (< 12 weeks) led to greater increases in adiponectin and IGF-1 and stronger reductions in TNF-α and IL-1β, suggesting a transient response. Women, unhealthy individuals, and those who were overweight or obese exhibited greater improvements than their counterparts. Anti-inflammatory effects were more pronounced when accompanied by decreases in body mass, fat mass, and improved glucose and lipid metabolism, but was not dependent on those changes.</div></div><div><h3>Conclusion</h3><div>Aerobic training is the most effective intervention, followed by resistance training, and at least 3 sessions per week (or twice a week for more than 24 weeks) are needed for metabolic and anti-inflammatory adaptations. This compendium provides a reference point for personalised exercise plans for treatment and prevention of chronic diseases—especially for older adults with metabolic conditions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102974"},"PeriodicalIF":12.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688936","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}
Pub Date : 2025-12-03DOI: 10.1016/j.arr.2025.102985
Haoxian Tang , Xiaojing Chen , Jingtao Huang , Qinglong Yang , Kunyao Liang , Xianghui Qiu , Junshaung Tang , Cuihong Tian , Nan Luo , Mengyue Lin , Xuan Zhang , Shiwan Wu , Xiulian Deng , Hanyuan Lin , Jianan Hong , Jiasheng Wen , Liwen Jiang , Pan Chen , Wenfeng Lin , Wenqi Chen , Yequn Chen
<div><h3>Background</h3><div>The global population is aging rapidly, extending into the oldest old. However, increased longevity does not always translate into enhanced health. While genetic and environmental factors influence lifespan, evidence indicates that targeted interventions can substantially enhance the likelihood of reaching 100 years. This study aimed to characterize disease and risk factor patterns among the oldest-old to identify actionable targets for promoting health and functional capacity in this rapidly growing population.</div></div><div><h3>Methods</h3><div>This study identified 18 countries with the largest populations aged 95 years and older using data from the Global Burden of Disease (GBD) 2023 study and the United Nations World Population Prospects 2024. Disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) from 1990 to 2023 were quantified, ranked, and visualized across three major cause categories (non-communicable, communicable and nutritional diseases, and injuries) and risk factors (behavioral, environmental/occupational, and metabolic) by using the GBD 2023 estimates. Temporal trends were assessed using estimated annual percentage change derived from log-linear regression models, calculated separately for periods before and after the COVID-19 pandemic peak. K-means clustering was employed to identify cross-country burden patterns, with the optimal number of clusters determined via the silhouette method. Temporal trends in health-adjusted life expectancy (HALE) were examined, and frontier analysis was applied to estimate the potential for further HALE improvement across countries.</div></div><div><h3>Results</h3><div>From 1990–2023, the absolute disease burden among individuals aged 95 + years increased more than fivefold, primarily driven by non-communicable diseases, accounting for ∼86 % of the total DALYs. Ischemic heart disease remained the leading cause, particularly for YLLs, followed by Alzheimer’s disease and other dementias, which predominated in YLDs, followed by stroke and chronic kidney disease. During the COVID-19 pandemic peak (2019–2021), mental health disorders, including depression and anxiety, demonstrated a marked increase. Cluster analysis in 2023 revealed two distinct national patterns: one dominated by acute cardiovascular conditions and the other by chronic multi-system diseases. Absolute burdens of metabolic, behavioral, and environmental/occupational risk factors increased over time, although their relative contributions declined; high systolic blood pressure (YLLs), high fasting plasma glucose (YLDs), and kidney dysfunction remained the leading risk factors. The average HALE increased from 1.86 years in 1990–2.16 years in 2019, declined during the pandemic, and partially recovered by 2023. Frontier analysis indicated nearly a twofold potential for further HALE improvement under current socioeconomic conditions.</div></div><div><h3>Conclusio
{"title":"Characterizing patterns in causes, risk factors, and life expectancy among the oldest old (aged 95+ years)","authors":"Haoxian Tang , Xiaojing Chen , Jingtao Huang , Qinglong Yang , Kunyao Liang , Xianghui Qiu , Junshaung Tang , Cuihong Tian , Nan Luo , Mengyue Lin , Xuan Zhang , Shiwan Wu , Xiulian Deng , Hanyuan Lin , Jianan Hong , Jiasheng Wen , Liwen Jiang , Pan Chen , Wenfeng Lin , Wenqi Chen , Yequn Chen","doi":"10.1016/j.arr.2025.102985","DOIUrl":"10.1016/j.arr.2025.102985","url":null,"abstract":"<div><h3>Background</h3><div>The global population is aging rapidly, extending into the oldest old. However, increased longevity does not always translate into enhanced health. While genetic and environmental factors influence lifespan, evidence indicates that targeted interventions can substantially enhance the likelihood of reaching 100 years. This study aimed to characterize disease and risk factor patterns among the oldest-old to identify actionable targets for promoting health and functional capacity in this rapidly growing population.</div></div><div><h3>Methods</h3><div>This study identified 18 countries with the largest populations aged 95 years and older using data from the Global Burden of Disease (GBD) 2023 study and the United Nations World Population Prospects 2024. Disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) from 1990 to 2023 were quantified, ranked, and visualized across three major cause categories (non-communicable, communicable and nutritional diseases, and injuries) and risk factors (behavioral, environmental/occupational, and metabolic) by using the GBD 2023 estimates. Temporal trends were assessed using estimated annual percentage change derived from log-linear regression models, calculated separately for periods before and after the COVID-19 pandemic peak. K-means clustering was employed to identify cross-country burden patterns, with the optimal number of clusters determined via the silhouette method. Temporal trends in health-adjusted life expectancy (HALE) were examined, and frontier analysis was applied to estimate the potential for further HALE improvement across countries.</div></div><div><h3>Results</h3><div>From 1990–2023, the absolute disease burden among individuals aged 95 + years increased more than fivefold, primarily driven by non-communicable diseases, accounting for ∼86 % of the total DALYs. Ischemic heart disease remained the leading cause, particularly for YLLs, followed by Alzheimer’s disease and other dementias, which predominated in YLDs, followed by stroke and chronic kidney disease. During the COVID-19 pandemic peak (2019–2021), mental health disorders, including depression and anxiety, demonstrated a marked increase. Cluster analysis in 2023 revealed two distinct national patterns: one dominated by acute cardiovascular conditions and the other by chronic multi-system diseases. Absolute burdens of metabolic, behavioral, and environmental/occupational risk factors increased over time, although their relative contributions declined; high systolic blood pressure (YLLs), high fasting plasma glucose (YLDs), and kidney dysfunction remained the leading risk factors. The average HALE increased from 1.86 years in 1990–2.16 years in 2019, declined during the pandemic, and partially recovered by 2023. Frontier analysis indicated nearly a twofold potential for further HALE improvement under current socioeconomic conditions.</div></div><div><h3>Conclusio","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102985"},"PeriodicalIF":12.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688923","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}
Pub Date : 2025-12-03DOI: 10.1016/j.arr.2025.102984
Rinku Shaha , Angel Godad
Huntington’s Disease (HD) is a neurodegenerative, genetic disorder that affects the brain and is caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in the huntingtin (HTT) gene exceeding 35 units. Further, the mutation occurs, which leads to the generation of mutant huntingtin (mHTT) protein, which is a toxic protein that damages the neurons and their functions, leading to disease progression. Phosphorylation, SUMOylation, O-GlcNAcylation, and ubiquitination are some of the post-translational modifications (PTMs) that affect the toxicity, location, and aggregation of this altered protein. The survival of neurons depends on autophagy, vesicle trafficking, transcriptional control, and mitochondrial function, all of which are disrupted by HTT. This protein tends to form aggregates, which disrupt vital neuronal functions and ultimately result in neuronal death, especially in the cortex and striatum. The three clinical manifestations of HD include mental health problems, cognitive impairment, and motor symptoms (bradykinesia, chorea). In this review, the HTT protein is examined, along with its normal functions, post-translational modifications, and role in HD pathogenesis. The therapeutic intervention under investigation includes PTM-targeted medications, which are those drugs that enhance neuroprotection and proteostasis, and gene silencing strategies such as antisense oligonucleotides and RNA interference. Disease models are being improved with several novel approaches, which include induced pluripotent stem cells (iPSCs) and CRISPR-based editing and preclinical models. By integrating these technologies, the mechanisms of the underlying disease have also been enhanced. The recent treatment approaches have also been explored by using molecular targets and diagnostic tools, including FANCD2 and FANCI-associated nuclease 1 (FAN1), which are genetic regulators of somatic CAG expansion; EPS8 dysregulation, which causes protein aggregation; and mismatch negativity (MMN), which is a brain response detected by EEG, a non-invasive biomarker for early cognitive impairment. These measures aim to slow down disease progression and improve the health and outcomes of patients.
{"title":"Huntingtin protein in health and Huntington’s disease: Molecular mechanisms, pathology and therapeutic strategies","authors":"Rinku Shaha , Angel Godad","doi":"10.1016/j.arr.2025.102984","DOIUrl":"10.1016/j.arr.2025.102984","url":null,"abstract":"<div><div>Huntington’s Disease (HD) is a neurodegenerative, genetic disorder that affects the brain and is caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in the huntingtin (HTT) gene exceeding 35 units. Further, the mutation occurs, which leads to the generation of mutant huntingtin (mHTT) protein, which is a toxic protein that damages the neurons and their functions, leading to disease progression. Phosphorylation, SUMOylation, O-GlcNAcylation, and ubiquitination are some of the post-translational modifications (PTMs) that affect the toxicity, location, and aggregation of this altered protein. The survival of neurons depends on autophagy, vesicle trafficking, transcriptional control, and mitochondrial function, all of which are disrupted by HTT. This protein tends to form aggregates, which disrupt vital neuronal functions and ultimately result in neuronal death, especially in the cortex and striatum. The three clinical manifestations of HD include mental health problems, cognitive impairment, and motor symptoms (bradykinesia, chorea). In this review, the HTT protein is examined, along with its normal functions, post-translational modifications, and role in HD pathogenesis. The therapeutic intervention under investigation includes PTM-targeted medications, which are those drugs that enhance neuroprotection and proteostasis, and gene silencing strategies such as antisense oligonucleotides and RNA interference. Disease models are being improved with several novel approaches, which include induced pluripotent stem cells (iPSCs) and CRISPR-based editing and preclinical models. By integrating these technologies, the mechanisms of the underlying disease have also been enhanced. The recent treatment approaches have also been explored by using molecular targets and diagnostic tools, including FANCD2 and FANCI-associated nuclease 1 (FAN1), which are genetic regulators of somatic CAG expansion; EPS8 dysregulation, which causes protein aggregation; and mismatch negativity (MMN), which is a brain response detected by EEG, a non-invasive biomarker for early cognitive impairment. These measures aim to slow down disease progression and improve the health and outcomes of patients.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102984"},"PeriodicalIF":12.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688922","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}
Pub Date : 2025-12-02DOI: 10.1016/j.arr.2025.102958
Yuze Wang , Hongyi Li , Qian Zhao , Xiang Li , Xuefan Bu , Chenye Ma , Zhihui Liu , Jinghua Yang , Tongwen Sun
Sepsis is a common and highly fatal condition in intensive care units and is one of the leading causes of death worldwide. As a clinically complex syndrome with intricate pathophysiology, early identification and assessment of sepsis remain challenging. Deeper insights at the molecular level are crucial for understanding the complex pathophysiological mechanisms, discovering new biomarkers, and improving prognosis. Post-translational modifications (PTMs) refer to the attachment of specific chemical groups to amino acid side chains through covalent, enzymatic, or non-enzymatic means, greatly expanding protein diversity and playing critical roles in many cellular signaling pathways. Here, we elucidate the regulatory roles of PTMs in sepsis pathways and key proteins, including immune response, late-stage inflammatory mediators, cellular metabolic reprogramming, and endothelial injury. We also summarize the progress in research on PTM-related sepsis biomarkers, covering diagnosis, prognosis, and organ dysfunction assessment, with a particular focus on the potential of glycosylation as a biomarker. Furthermore, we review current methodologies for studying PTMs. Continued focus on PTMs will pave the way for new possibilities in sepsis research and treatment.
{"title":"Protein post-translational modifications in sepsis: Molecular mechanisms and biomarkers","authors":"Yuze Wang , Hongyi Li , Qian Zhao , Xiang Li , Xuefan Bu , Chenye Ma , Zhihui Liu , Jinghua Yang , Tongwen Sun","doi":"10.1016/j.arr.2025.102958","DOIUrl":"10.1016/j.arr.2025.102958","url":null,"abstract":"<div><div>Sepsis is a common and highly fatal condition in intensive care units and is one of the leading causes of death worldwide. As a clinically complex syndrome with intricate pathophysiology, early identification and assessment of sepsis remain challenging. Deeper insights at the molecular level are crucial for understanding the complex pathophysiological mechanisms, discovering new biomarkers, and improving prognosis. Post-translational modifications (PTMs) refer to the attachment of specific chemical groups to amino acid side chains through covalent, enzymatic, or non-enzymatic means, greatly expanding protein diversity and playing critical roles in many cellular signaling pathways. Here, we elucidate the regulatory roles of PTMs in sepsis pathways and key proteins, including immune response, late-stage inflammatory mediators, cellular metabolic reprogramming, and endothelial injury. We also summarize the progress in research on PTM-related sepsis biomarkers, covering diagnosis, prognosis, and organ dysfunction assessment, with a particular focus on the potential of glycosylation as a biomarker. Furthermore, we review current methodologies for studying PTMs. Continued focus on PTMs will pave the way for new possibilities in sepsis research and treatment.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102958"},"PeriodicalIF":12.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679716","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}
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