Pub Date : 2026-01-01Epub Date: 2025-12-12DOI: 10.1016/j.arr.2025.102995
Yan Lv , Xv-Shen Ding , Li Gao , Zheng Han , Chen-Xi Feng , Yang-Ni Li , Yu-Fei Wang , Qian Yang , David K. Simon , Xue-lian Wang , Yan Qu , Bao Wang
The accumulation of α-synuclein (α-syn) is a key pathophysiological feature of Parkinson’s disease (PD), and one contributing factor to this aggregation is impaired clearance mechanisms. Recent research has identified the glymphatic system as the brain’s intrinsic waste clearance pathway. This review examines glymphatic dysfunction in PD, with a focus on its impact on α-syn clearance and neurodegeneration. We summarize current evidence showing that disrupted aquaporin-4 (AQP4) polarization, reduced meningeal lymphatic drainage, and sleep disturbances collectively impair glymphatic flow, thereby promoting α-syn aggregation and dopaminergic neuronal loss. We also review emerging neuroimaging approaches, including the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index, enlarged perivascular spaces (EPVSs) and choroid plexus volume (CPV), which increasingly enable in vivo evaluation of glymphatic dysfunction and show correlations with motor severity and cognitive decline. In addition, we discuss potential therapeutic approaches aimed at restoring glymphatic function, including photobiomodulation, pharmacological AQP4 modulation, sleep based interventions, and surgical interventions like deep cervical lymphaticovenular anastomosis (dcLVA). Although these strategies show promise in preclinical studies, their clinical translation remains limited. By integrating insights from glymphatic biology, neuroimaging, and therapeutic development, this review highlights new avenues for PD management and underscores the glymphatic system as a promising therapeutic target for modifying disease progression.
{"title":"Glymphatic dysfunction in Parkinson's disease: Aging-associated impairments, imaging biomarkers, and therapeutic strategies","authors":"Yan Lv , Xv-Shen Ding , Li Gao , Zheng Han , Chen-Xi Feng , Yang-Ni Li , Yu-Fei Wang , Qian Yang , David K. Simon , Xue-lian Wang , Yan Qu , Bao Wang","doi":"10.1016/j.arr.2025.102995","DOIUrl":"10.1016/j.arr.2025.102995","url":null,"abstract":"<div><div>The accumulation of α-synuclein (α-syn) is a key pathophysiological feature of Parkinson’s disease (PD), and one contributing factor to this aggregation is impaired clearance mechanisms. Recent research has identified the glymphatic system as the brain’s intrinsic waste clearance pathway. This review examines glymphatic dysfunction in PD, with a focus on its impact on α-syn clearance and neurodegeneration. We summarize current evidence showing that disrupted aquaporin-4 (AQP4) polarization, reduced meningeal lymphatic drainage, and sleep disturbances collectively impair glymphatic flow, thereby promoting α-syn aggregation and dopaminergic neuronal loss. We also review emerging neuroimaging approaches, including the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index, enlarged perivascular spaces (EPVSs) and choroid plexus volume (CPV), which increasingly enable in vivo evaluation of glymphatic dysfunction and show correlations with motor severity and cognitive decline. In addition, we discuss potential therapeutic approaches aimed at restoring glymphatic function, including photobiomodulation, pharmacological AQP4 modulation, sleep based interventions, and surgical interventions like deep cervical lymphaticovenular anastomosis (dcLVA). Although these strategies show promise in preclinical studies, their clinical translation remains limited. By integrating insights from glymphatic biology, neuroimaging, and therapeutic development, this review highlights new avenues for PD management and underscores the glymphatic system as a promising therapeutic target for modifying disease progression.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102995"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758574","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 : 2026-01-01Epub 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":"2026-01-01","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 : 2026-01-01Epub Date: 2025-08-25DOI: 10.1016/j.arr.2025.102879
Aurgha Kamal Bhandari , Aman Singh Dhami , Rishi Thanvanthan Hemanthkumar , Nishant Mishra , Beula Joslyn , Sindhujit Roy , Jaisri Srinivasan , Kailash Prasad Prajapati , Karunakar Kar , Bibin Gnanadhason Anand
Microtubule-associated protein tau (MAP) is a crucial component for cellular cytoskeleton stability. However, upon hyperphosphorylation, these tau proteins detach from microtubules, leading to the genesis of clumpy fibrillar-rich β or paired helical filamental structures known as amyloids. Such deposits predispose a multitude of fatal disorders, including Alzheimer’s Disease. The initial event behind such genesis is still a mystery. Today, numerous research studies try to untangle the initial events that lead to the formation of homogeneous and heterogeneous multicomponent plaques in AD, which remain elusive. Since tauopathies are linked to neurodegeneration and the tau tangles damage the neurons and glia, the question of what events trigger the phosphorylation of tau, leading to the molecular crowding of tau repeats, remains largely unknown. Such molecular crowding or initial events before primary nucleation are driven by liquid-liquid phase separation (LLPS), where tau or tau, along with various biomolecules forming dynamic interaction networks leading to the formation of homotypic and heterotypic condensates, ultimately result in co-existing phases before transitioning to nucleation. This review has explored the fundamental principles of LLPS in tau, aiming to establish a link between tau condensates and their pathogenic forms followed by the factors that modulate its phase transition. Our review hopes to provide the scientific community with a strong foundation to build upon, to understand the importance and gravity of studying tau phase separation and the new opportunities it hides within itself.
{"title":"Biomolecular phase separation of microtubule-associated protein tau and its role in the genesis of brain disorders","authors":"Aurgha Kamal Bhandari , Aman Singh Dhami , Rishi Thanvanthan Hemanthkumar , Nishant Mishra , Beula Joslyn , Sindhujit Roy , Jaisri Srinivasan , Kailash Prasad Prajapati , Karunakar Kar , Bibin Gnanadhason Anand","doi":"10.1016/j.arr.2025.102879","DOIUrl":"10.1016/j.arr.2025.102879","url":null,"abstract":"<div><div>Microtubule-associated protein tau (MAP) is a crucial component for cellular cytoskeleton stability. However, upon hyperphosphorylation, these tau proteins detach from microtubules, leading to the genesis of clumpy fibrillar-rich β or paired helical filamental structures known as amyloids. Such deposits predispose a multitude of fatal disorders, including Alzheimer’s Disease. The initial event behind such genesis is still a mystery. Today, numerous research studies try to untangle the initial events that lead to the formation of homogeneous and heterogeneous multicomponent plaques in AD, which remain elusive. Since tauopathies are linked to neurodegeneration and the tau tangles damage the neurons and glia, the question of what events trigger the phosphorylation of tau, leading to the molecular crowding of tau repeats, remains largely unknown. Such molecular crowding or initial events before primary nucleation are driven by liquid-liquid phase separation (LLPS), where tau or tau, along with various biomolecules forming dynamic interaction networks leading to the formation of homotypic and heterotypic condensates, ultimately result in co-existing phases before transitioning to nucleation. This review has explored the fundamental principles of LLPS in tau, aiming to establish a link between tau condensates and their pathogenic forms followed by the factors that modulate its phase transition. Our review hopes to provide the scientific community with a strong foundation to build upon, to understand the importance and gravity of studying tau phase separation and the new opportunities it hides within itself.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102879"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982072","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 : 2026-01-01Epub 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":"2026-01-01","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 : 2026-01-01Epub Date: 2025-11-05DOI: 10.1016/j.arr.2025.102935
Maria Elisa Giuliani , Chiara Giordani , Gianmarco Bertoni , Emanuele Francini , Giorgia Bigossi , Giovanni Lai , Serena Marcozzi , Sunday Segun Alimi , Davide Perini , Andrea Piccinini , Sara Ristori , Elisa Bientinesi , Francesca Barone , Maurizio Cardelli , Cesare Indiveri , Mariafrancesca Scalise , Daniela Monti , Marco Malavolta
Aging is a natural, multifactorial biological process characterized by progressive cellular and tissue damage in response to various stressors, leading to functional decline that often affects multiple organs, contributing to the development of age-related diseases. Although life expectancy has increased significantly, age-related conditions have become the leading causes of impairment and disability in the elderly, becoming a major global health concern. This highlights the need for innovative, multitarget strategies to modulate the aging process and extend healthspan. In recent years, researchers have explored natural solutions to counteract the hallmarks of aging. Among these, marine-derived molecules represent an up-and-coming niche of bioactive compounds, distinguished by their unique structural diversity and multifunctional properties. Marine products are increasingly studied for their antioxidant, anti-inflammatory and cytoprotective properties, targeting key pathways involved in aging, such as cellular senescence, genomic instability, impaired autophagy, and chronic inflammation. In this review, we aim to (i) explore the field of marine-derived bioactive molecules which demonstrated effects on lifespan extension, (ii) summarize studies showing their capacity to target one or more hallmarks of aging, (iii) highlight those that exhibit therapeutic potential in age-related diseases – including neurodegenerative, cardiovascular, metabolic, cancer, musculoskeletal, and chronic pulmonary disorders. Their multitarget activity makes them attractive candidates for the prevention or treatment of age-related diseases, and several have shown promising results in preclinical studies. However, only a limited number of these compounds have progressed to late-stage clinical trials, highlighting the need for further translational research, which may pave the way for novel anti-aging therapeutic strategies.
{"title":"The potential of marine-derived compounds in geroscience","authors":"Maria Elisa Giuliani , Chiara Giordani , Gianmarco Bertoni , Emanuele Francini , Giorgia Bigossi , Giovanni Lai , Serena Marcozzi , Sunday Segun Alimi , Davide Perini , Andrea Piccinini , Sara Ristori , Elisa Bientinesi , Francesca Barone , Maurizio Cardelli , Cesare Indiveri , Mariafrancesca Scalise , Daniela Monti , Marco Malavolta","doi":"10.1016/j.arr.2025.102935","DOIUrl":"10.1016/j.arr.2025.102935","url":null,"abstract":"<div><div>Aging is a natural, multifactorial biological process characterized by progressive cellular and tissue damage in response to various stressors, leading to functional decline that often affects multiple organs, contributing to the development of age-related diseases. Although life expectancy has increased significantly, age-related conditions have become the leading causes of impairment and disability in the elderly, becoming a major global health concern. This highlights the need for innovative, multitarget strategies to modulate the aging process and extend healthspan. In recent years, researchers have explored natural solutions to counteract the hallmarks of aging. Among these, marine-derived molecules represent an up-and-coming niche of bioactive compounds, distinguished by their unique structural diversity and multifunctional properties. Marine products are increasingly studied for their antioxidant, anti-inflammatory and cytoprotective properties, targeting key pathways involved in aging, such as cellular senescence, genomic instability, impaired autophagy, and chronic inflammation. In this review, we aim to (i) explore the field of marine-derived bioactive molecules which demonstrated effects on lifespan extension, (ii) summarize studies showing their capacity to target one or more hallmarks of aging, (iii) highlight those that exhibit therapeutic potential in age-related diseases – including neurodegenerative, cardiovascular, metabolic, cancer, musculoskeletal, and chronic pulmonary disorders. Their multitarget activity makes them attractive candidates for the prevention or treatment of age-related diseases, and several have shown promising results in preclinical studies. However, only a limited number of these compounds have progressed to late-stage clinical trials, highlighting the need for further translational research, which may pave the way for novel anti-aging therapeutic strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102935"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472595","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 : 2026-01-01Epub Date: 2025-10-17DOI: 10.1016/j.arr.2025.102924
Meichao Cheng , Jingting Ni , Fenghu Liu , Shun Wang
Background
This meta-analysis aims to evaluate the effects of exercise interventions on fall rates and fall risk in older adults and identify the most effective exercise types and doses for fall prevention.
Methods
Systematic searches of PubMed, Web of Science, SPORTDiscus, PsychINFO, Embase, and Scopus databases were conducted from the beginning of database construction through November 2024. Studies were included if they were randomized controlled trials (RCTs) of exercise interventions for older adults. Paired, network, and dose-response meta-analyses were conducted using random-effects models for outcomes of falls behavior in older adults.
Results
A total of 21 RCTs involving 3387 participants were included in this study. The results indicated that the ranking of intervention effectiveness in reducing fall-related behaviors among older adults, based on SUCRA values, was as follows: Falls Management Exercise Programme (FaME) (68.56 %) > Otago Exercise Program (OEP) (57.58 %) > aquatic exercise (43.96 %) > Tai Chi (41.52 %) > balance training (0.58 %). In addition, a reverse U-shaped dose-response relationship was observed between total exercise dose and fall-related outcomes in older adults, with the optimal response occurring at approximately 420 MET·min/week. Notably, the optimal dose varied across different exercise modalities.
Conclusions
The study identified the relative effectiveness of different exercise interventions in improving fall-related outcomes among older adults. Falls Management Exercise Programme (FaME) was found to be the most effective adjunctive intervention, followed by Otago Exercise Program (OEP), aquatic exercise, Tai Chi, and balance training. Providing the most effective exercise strategies may enhance fall prevention in older adults, even when the exercise dose falls below the thresholds recommended by the WHO guidelines.
背景：本荟萃分析旨在评估运动干预对老年人跌倒率和跌倒风险的影响，并确定预防跌倒最有效的运动类型和剂量。方法：从建库之初至2024年11月，系统检索PubMed、Web of Science、SPORTDiscus、PsychINFO、Embase、Scopus等数据库。如果是老年人运动干预的随机对照试验（rct），则纳入研究。使用随机效应模型对老年人跌倒行为的结果进行配对、网络和剂量-反应荟萃分析。结果：本研究共纳入21项随机对照试验，共3387名受试者。结果表明，基于SUCRA值，老年人减少跌倒相关行为的干预效果排序为：跌倒管理运动计划（FaME）(68.56%) >奥塔哥运动计划（OEP）(57.58%) >水上运动(43.96%)>太极(41.52%)>平衡训练（0.58%）。此外，在老年人中，总运动剂量和跌倒相关结果之间观察到反向u型剂量-反应关系，最佳反应发生在大约420 MET·min/周。值得注意的是，最佳剂量因不同的运动方式而异。结论：该研究确定了不同运动干预在改善老年人跌倒相关结果方面的相对有效性。跌倒管理运动计划（FaME）是最有效的辅助干预措施，其次是奥塔哥运动计划（OEP）、水上运动、太极和平衡训练。提供最有效的运动策略可以加强老年人的跌倒预防，即使运动剂量低于世界卫生组织指南建议的阈值。
{"title":"Optimal type and dose of exercise to improve fall behavior in older adults: A systematic evaluation and network meta-analysis","authors":"Meichao Cheng , Jingting Ni , Fenghu Liu , Shun Wang","doi":"10.1016/j.arr.2025.102924","DOIUrl":"10.1016/j.arr.2025.102924","url":null,"abstract":"<div><h3>Background</h3><div>This meta-analysis aims to evaluate the effects of exercise interventions on fall rates and fall risk in older adults and identify the most effective exercise types and doses for fall prevention.</div></div><div><h3>Methods</h3><div>Systematic searches of PubMed, Web of Science, SPORTDiscus, PsychINFO, Embase, and Scopus databases were conducted from the beginning of database construction through November 2024. Studies were included if they were randomized controlled trials (RCTs) of exercise interventions for older adults. Paired, network, and dose-response meta-analyses were conducted using random-effects models for outcomes of falls behavior in older adults.</div></div><div><h3>Results</h3><div>A total of 21 RCTs involving 3387 participants were included in this study. The results indicated that the ranking of intervention effectiveness in reducing fall-related behaviors among older adults, based on SUCRA values, was as follows: Falls Management Exercise Programme (FaME) (68.56 %) > Otago Exercise Program (OEP) (57.58 %) > aquatic exercise (43.96 %) > Tai Chi (41.52 %) > balance training (0.58 %). In addition, a reverse U-shaped dose-response relationship was observed between total exercise dose and fall-related outcomes in older adults, with the optimal response occurring at approximately 420 MET·min/week. Notably, the optimal dose varied across different exercise modalities.</div></div><div><h3>Conclusions</h3><div>The study identified the relative effectiveness of different exercise interventions in improving fall-related outcomes among older adults. Falls Management Exercise Programme (FaME) was found to be the most effective adjunctive intervention, followed by Otago Exercise Program (OEP), aquatic exercise, Tai Chi, and balance training. Providing the most effective exercise strategies may enhance fall prevention in older adults, even when the exercise dose falls below the thresholds recommended by the WHO guidelines.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102924"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331078","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 : 2026-01-01Epub Date: 2025-11-27DOI: 10.1016/j.arr.2025.102963
Azliyana Azizan
The adoption of digital therapeutics among older adults presents both opportunities and challenges in modern healthcare. While these technologies enhance disease management, autonomy, and quality of life, engagement remains hindered by cognitive, emotional, systemic, and sociocultural barriers. This narrative review synthesizes findings from 76 peer-reviewed studies identified through Scopus and Web of Science (2010–2024) to examine key factors influencing geriatric engagement with digital therapeutics.
Findings
indicate that technological illiteracy, privacy concerns, usability challenges, and mistrust in digital platforms significantly limit adoption. Additionally, cultural attitudes, generational skepticism, and infrastructural limitations exacerbate digital disparities. Conversely, personalized health benefits, caregiver and peer support, and intuitive design features serve as key motivators for adoption and sustained engagement.
To enhance digital inclusion, this review highlights the need for user-centered design principles, tailored digital literacy programs, and systemic policy interventions, such as broadband expansion and privacy safeguards.
Future research should explore longitudinal engagement patterns, culturally adaptive digital interventions, and the integration of behavioral and technological frameworks to optimize geriatric digital health solutions. Addressing these factors will be essential to ensuring equitable, inclusive, and effective digital therapeutics for aging populations worldwide
在老年人中采用数字疗法对现代医疗保健提出了机遇和挑战。虽然这些技术增强了疾病管理、自主性和生活质量，但参与仍然受到认知、情感、系统和社会文化障碍的阻碍。本叙述性综述综合了通过Scopus和Web of Science（2010-2024）确定的76项同行评议研究的结果，以检查影响老年人参与数字治疗的关键因素。研究结果表明，技术文盲、隐私问题、可用性挑战和对数字平台的不信任极大地限制了采用。此外，文化态度、代际怀疑和基础设施限制加剧了数字差距。相反，个性化的健康福利、照顾者和同伴支持以及直观的设计功能是采用和持续参与的关键激励因素。为加强数字包容，本综述强调需要制定以用户为中心的设计原则、量身定制的数字扫盲计划以及宽带扩展和隐私保护等系统性政策干预措施。未来的研究应探索纵向参与模式、文化适应性数字干预以及行为和技术框架的整合，以优化老年数字健康解决方案。解决这些因素对于确保为全球老龄化人口提供公平、包容和有效的数字治疗至关重要
{"title":"Barriers and motivators of geriatric engagement in digital therapeutics: A narrative review","authors":"Azliyana Azizan","doi":"10.1016/j.arr.2025.102963","DOIUrl":"10.1016/j.arr.2025.102963","url":null,"abstract":"<div><div>The adoption of digital therapeutics among older adults presents both opportunities and challenges in modern healthcare. While these technologies enhance disease management, autonomy, and quality of life, engagement remains hindered by cognitive, emotional, systemic, and sociocultural barriers. This narrative review synthesizes findings from 76 peer-reviewed studies identified through Scopus and Web of Science (2010–2024) to examine key factors influencing geriatric engagement with digital therapeutics.</div></div><div><h3>Findings</h3><div>indicate that technological illiteracy, privacy concerns, usability challenges, and mistrust in digital platforms significantly limit adoption. Additionally, cultural attitudes, generational skepticism, and infrastructural limitations exacerbate digital disparities. Conversely, personalized health benefits, caregiver and peer support, and intuitive design features serve as key motivators for adoption and sustained engagement.</div><div>To enhance digital inclusion, this review highlights the need for user-centered design principles, tailored digital literacy programs, and systemic policy interventions, such as broadband expansion and privacy safeguards.</div><div>Future research should explore longitudinal engagement patterns, culturally adaptive digital interventions, and the integration of behavioral and technological frameworks to optimize geriatric digital health solutions. Addressing these factors will be essential to ensuring equitable, inclusive, and effective digital therapeutics for aging populations worldwide</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102963"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625223","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 : 2026-01-01Epub Date: 2025-10-24DOI: 10.1016/j.arr.2025.102927
Huiwen Lei , Xiaohua Chen , Longzhu Ruan , Xuena Liu , Fei Ye , Kejing Li , Wei Cheng , Boyi Yu , Qiang Li , Cuixia Di
Neurofibrillary tangles formed by abnormal hyperphosphorylation of tau are a hallmark neuropathological feature of Alzheimer's disease (AD). Beyond phosphorylation, tau undergoes diverse post-translational modifications (PTMs), which modulate its structural conformation and functional properties, driving pathological aggregation and contributing to neurodegeneration. Exploring the mechanisms underlying tau PTMs has yielded critical insights into the development of therapeutic interventions and diagnostic tools for tauopathies, particularly AD. Based on this, the structural characteristics and functional roles of tau are briefly described. Subsequently, we delve into how tau PTMs act as drivers of AD pathogenesis, with particular emphasis on the individual contributions and therapeutic potential of phosphorylation, glycosylation, acetylation, and other PTMs. The cross-talk between PTMs is also reviewed. Importantly, discussion extends to how these PTMs instigate pathological cascades, promoting tau aggregation, propagation, and neurotoxicity. Furthermore, we highlight emerging therapeutic strategies targeting tau PTMs through several distinct directions. Ultimately, we evaluate the promising potential of tau PTM-based biomarkers for AD diagnosis. Therefore, a comprehensive understanding of tau PTMs offers profound implications for unraveling the pathogenesis of AD and paving the way for innovative therapeutic and diagnostic approaches.
{"title":"Tau post-translational modifications in Alzheimer's disease: Insights into pathogenesis, therapeutic strategies, and diagnostic advances","authors":"Huiwen Lei , Xiaohua Chen , Longzhu Ruan , Xuena Liu , Fei Ye , Kejing Li , Wei Cheng , Boyi Yu , Qiang Li , Cuixia Di","doi":"10.1016/j.arr.2025.102927","DOIUrl":"10.1016/j.arr.2025.102927","url":null,"abstract":"<div><div>Neurofibrillary tangles formed by abnormal hyperphosphorylation of tau are a hallmark neuropathological feature of Alzheimer's disease (AD). Beyond phosphorylation, tau undergoes diverse post-translational modifications (PTMs), which modulate its structural conformation and functional properties, driving pathological aggregation and contributing to neurodegeneration. Exploring the mechanisms underlying tau PTMs has yielded critical insights into the development of therapeutic interventions and diagnostic tools for tauopathies, particularly AD. Based on this, the structural characteristics and functional roles of tau are briefly described. Subsequently, we delve into how tau PTMs act as drivers of AD pathogenesis, with particular emphasis on the individual contributions and therapeutic potential of phosphorylation, glycosylation, acetylation, and other PTMs. The cross-talk between PTMs is also reviewed. Importantly, discussion extends to how these PTMs instigate pathological cascades, promoting tau aggregation, propagation, and neurotoxicity. Furthermore, we highlight emerging therapeutic strategies targeting tau PTMs through several distinct directions. Ultimately, we evaluate the promising potential of tau PTM-based biomarkers for AD diagnosis. Therefore, a comprehensive understanding of tau PTMs offers profound implications for unraveling the pathogenesis of AD and paving the way for innovative therapeutic and diagnostic approaches.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102927"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417921","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 : 2026-01-01Epub Date: 2025-12-20DOI: 10.1016/j.arr.2025.103002
Susan Li , Jacinta Lin , Sarah N. Hilmer , Janani Thillainadesan
Background
Frailty is a prevalent and significant health condition in older adults, and mobile health applications (MHAs) offer a promising avenue to enhance screening and early detection of frailty allowing healthcare professionals to enact timely interventions. This scoping review aimed to synthesise the features of existing MHAs on frailty and assess their quality.
Methods
Two independent researchers searched the Apple App Store and Google Play Store using keywords “Frailty”, “Frail”, “Geriatrics”, “Geriatric”, and “Older Adults” between July and August 2023, with an updated search conducted from June to July 2025. Application quality was assessed using the Mobile App Rating Scale, which evaluates apps in four domains: engagement, functionality, aesthetics and information.
Results
Fourteen MHAs met the inclusion criteria. Twenty clinical frailty tools were referenced across the applications. Content included frailty identification (n = 13), definition (n = 6), management (n = 6), risk factors (n = 4), prognosis (n = 2), and screening (n = 1). All applications targeted healthcare professionals. Few targeted carers (n = 2) or patients (n = 1). Most applications (n = 13) included interactive features. Quality scores were highest for functionality and lowest for engagement.
Conclusion
While MHAs have potential to assist healthcare professionals to identify frailty in older adults, their limited focus on patient education, carer support, and frailty management highlights the need for further development. Future studies should evaluate app effectiveness, for example in improving clinicians’ ability to identify and manage frailty and explore ways to integrate MHAs into clinical practice to enable timely, effective interventions for frailty.
{"title":"Mobile health applications on frailty: A scoping review","authors":"Susan Li , Jacinta Lin , Sarah N. Hilmer , Janani Thillainadesan","doi":"10.1016/j.arr.2025.103002","DOIUrl":"10.1016/j.arr.2025.103002","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is a prevalent and significant health condition in older adults, and mobile health applications (MHAs) offer a promising avenue to enhance screening and early detection of frailty allowing healthcare professionals to enact timely interventions. This scoping review aimed to synthesise the features of existing MHAs on frailty and assess their quality.</div></div><div><h3>Methods</h3><div>Two independent researchers searched the Apple App Store and Google Play Store using keywords “Frailty”, “Frail”, “Geriatrics”, “Geriatric”, and “Older Adults” between July and August 2023, with an updated search conducted from June to July 2025. Application quality was assessed using the Mobile App Rating Scale, which evaluates apps in four domains: engagement, functionality, aesthetics and information.</div></div><div><h3>Results</h3><div>Fourteen MHAs met the inclusion criteria. Twenty clinical frailty tools were referenced across the applications. Content included frailty identification (n = 13), definition (n = 6), management (n = 6), risk factors (n = 4), prognosis (n = 2), and screening (n = 1). All applications targeted healthcare professionals. Few targeted carers (n = 2) or patients (n = 1). Most applications (n = 13) included interactive features. Quality scores were highest for functionality and lowest for engagement.</div></div><div><h3>Conclusion</h3><div>While MHAs have potential to assist healthcare professionals to identify frailty in older adults, their limited focus on patient education, carer support, and frailty management highlights the need for further development. Future studies should evaluate app effectiveness, for example in improving clinicians’ ability to identify and manage frailty and explore ways to integrate MHAs into clinical practice to enable timely, effective interventions for frailty.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 103002"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812358","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}
Cardiovascular diseases (CVDs) continue to rise at an alarming rate, contributing to millions of deaths globally. Among them, myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of mortality. Despite extensive research, MI remains incurable, and its complete eradication has yet to be achieved. Mitochondria play a central role in the pathogenesis and potential treatment of MI, and recent studies have identified mitochondrial microRNAs (mito-miRs) as promising molecular regulators. Although the precise mechanisms of mito-miRs remain incompletely understood, emerging evidence suggests their involvement in regulating mitochondrial metabolism, dynamics, ROS production, bioenergetics, and mitochondrial biogenesis. Additionally, mito-miRs influence several forms of programmed cell death, including apoptosis, necrosis, ferroptosis, and pyroptosis. The exact processes governing the translocation of these miRNAs into mitochondria and their intracellular actions remain elusive. Notably, specific miRNAs have been shown to target key cardiac cell types, including cardiomyocytes, endothelial cells, and fibroblasts. Deciphering their mechanistic roles could enable the development of targeted mito-miRNA-based therapeutics. Moreover, their therapeutic efficacy may be enhanced by integrating mito-miRs with stem cell therapies and bioactive compounds, particularly when delivered via nanoparticle-based formulations to ensure targeted delivery within the cardiac microenvironment.
{"title":"Targeting mitochondrial microRNAs in cardiovascular pathologies: A new frontier in precision cardiology","authors":"Satinder Kaur , Gurjit Kaur Bhatti , Naina Khullar , Jasvinder Singh Bhatti","doi":"10.1016/j.arr.2025.102920","DOIUrl":"10.1016/j.arr.2025.102920","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) continue to rise at an alarming rate, contributing to millions of deaths globally. Among them, myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of mortality. Despite extensive research, MI remains incurable, and its complete eradication has yet to be achieved. Mitochondria play a central role in the pathogenesis and potential treatment of MI, and recent studies have identified mitochondrial microRNAs (mito-miRs) as promising molecular regulators. Although the precise mechanisms of mito-miRs remain incompletely understood, emerging evidence suggests their involvement in regulating mitochondrial metabolism, dynamics, ROS production, bioenergetics, and mitochondrial biogenesis. Additionally, mito-miRs influence several forms of programmed cell death, including apoptosis, necrosis, ferroptosis, and pyroptosis. The exact processes governing the translocation of these miRNAs into mitochondria and their intracellular actions remain elusive. Notably, specific miRNAs have been shown to target key cardiac cell types, including cardiomyocytes, endothelial cells, and fibroblasts. Deciphering their mechanistic roles could enable the development of targeted mito-miRNA-based therapeutics. Moreover, their therapeutic efficacy may be enhanced by integrating mito-miRs with stem cell therapies and bioactive compounds, particularly when delivered via nanoparticle-based formulations to ensure targeted delivery within the cardiac microenvironment.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102920"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318930","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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