Pub Date : 2026-01-03DOI: 10.1016/j.arr.2026.103009
Yuan-Yuan Li , Franklin R. Tay
Reprogramming of somatic cells into induced pluripotent stem cells through the introduction of transcription factors Oct3/4, Sox2, Klf4, and c-Myc (OSKM) represents a landmark advance in regenerative biology. Building on this foundation, partial reprogramming can help reset epigenetic age. It further opens opportunities to treat degenerative diseases without the tumorigenic risks associated with full pluripotency. The review advances the field in three ways: it links lineage-preserving partial reprogramming to quantifiable rejuvenation endpoints; defines mesenchymal drift as an age- and disease-associated trajectory amenable to reversal; and maps strategies beyond OSKM, including small-molecule programs and CRISPR-based control circuits. Convergent phenotypes are surveyed in nervous, metabolic, musculoskeletal, and craniofacial systems, with emphasis on improved tissue repair and regeneration. A translational checklist is proposed that emphasizes schedule, delivery, and safety pharmacology to guide rigorous preclinical studies and de-risk early clinical entry points for partial reprogramming therapies.
{"title":"The epigenetic rejuvenation promise: Partial reprogramming as a therapeutic strategy for aging and disease","authors":"Yuan-Yuan Li , Franklin R. Tay","doi":"10.1016/j.arr.2026.103009","DOIUrl":"10.1016/j.arr.2026.103009","url":null,"abstract":"<div><div>Reprogramming of somatic cells into induced pluripotent stem cells through the introduction of transcription factors Oct3/4, Sox2, Klf4, and c-Myc (OSKM) represents a landmark advance in regenerative biology. Building on this foundation, partial reprogramming can help reset epigenetic age. It further opens opportunities to treat degenerative diseases without the tumorigenic risks associated with full pluripotency. The review advances the field in three ways: it links lineage-preserving partial reprogramming to quantifiable rejuvenation endpoints; defines mesenchymal drift as an age- and disease-associated trajectory amenable to reversal; and maps strategies beyond OSKM, including small-molecule programs and CRISPR-based control circuits. Convergent phenotypes are surveyed in nervous, metabolic, musculoskeletal, and craniofacial systems, with emphasis on improved tissue repair and regeneration. A translational checklist is proposed that emphasizes schedule, delivery, and safety pharmacology to guide rigorous preclinical studies and de-risk early clinical entry points for partial reprogramming therapies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103009"},"PeriodicalIF":12.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907459","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 : 2026-01-01DOI: 10.1016/j.arr.2025.103003
Chiara Bontempo , Lucio Publio Gallo , Marco Mattiacci , Sabrina Valente , Annalisa Astolfi , Maria Conte , Gaetano La Manna , Gianandrea Pasquinelli , Mauro Gargiulo , Fabiola Olivieri , Miriam Capri
Surfactant proteins, particularly SP-A and SP-D, S100 family members and fibronectin belong to the group of so-called stress-related molecules and share the characteristic of being expressed at anatomical barriers such as the skin, pulmonary/respiratory epithelia, and the intestinal tract. In this context, they constitute part of the body’s first line of defence, acting in concert with immune cells to counter a broad spectrum of external and internal stressors (exposomes), potentially fuelling chronic low-grade inflammation (inflammaging). The levels of the above-mentioned molecules in the blood or local tissues result altered in a range of age-associated pathologies and have been proposed as potential diagnostic/prognostic biomarkers, although they generally lack specificity for a single pathological condition. Evidence from in silico analyses further suggests that most of these molecules may be regulated by members of the microRNA-29 family, pointing towards hierarchical epigenetic mechanisms that merit detailed investigation as potential contributors to ageing-related biomarker signatures. Despite research advances, the identification of robust biomarkers capable of predicting disease onset at the individual level, an essential prerequisite for precise geromedicine, remains an elusive goal in clinical practice. Although individuals differ biologically, this does not preclude the existence of overarching principles that could be reflected in hierarchical biomarkers. Within this framework, a pragmatic strategy for immediate application may involve the systematic use of currently available longitudinal data, for example, from hospitalised patients or through dedicated software programs utilised by general practitioners.
{"title":"Barrier breakdown in ageing and age-related diseases: The potential role of hierarchical epigenetic control of microRNAs on surfactant collectins, S100 alarmins and fibronectin","authors":"Chiara Bontempo , Lucio Publio Gallo , Marco Mattiacci , Sabrina Valente , Annalisa Astolfi , Maria Conte , Gaetano La Manna , Gianandrea Pasquinelli , Mauro Gargiulo , Fabiola Olivieri , Miriam Capri","doi":"10.1016/j.arr.2025.103003","DOIUrl":"10.1016/j.arr.2025.103003","url":null,"abstract":"<div><div>Surfactant proteins, particularly SP-A and SP-D, S100 family members and fibronectin belong to the group of so-called stress-related molecules and share the characteristic of being expressed at anatomical barriers such as the skin, pulmonary/respiratory epithelia, and the intestinal tract. In this context, they constitute part of the body’s first line of defence, acting in concert with immune cells to counter a broad spectrum of external and internal stressors (exposomes), potentially fuelling chronic low-grade inflammation (inflammaging). The levels of the above-mentioned molecules in the blood or local tissues result altered in a range of age-associated pathologies and have been proposed as potential diagnostic/prognostic biomarkers, although they generally lack specificity for a single pathological condition. Evidence from in silico analyses further suggests that most of these molecules may be regulated by members of the microRNA-29 family, pointing towards hierarchical epigenetic mechanisms that merit detailed investigation as potential contributors to ageing-related biomarker signatures. Despite research advances, the identification of robust biomarkers capable of predicting disease onset at the individual level, an essential prerequisite for precise geromedicine, remains an elusive goal in clinical practice. Although individuals differ biologically, this does not preclude the existence of overarching principles that could be reflected in hierarchical biomarkers. Within this framework, a pragmatic strategy for immediate application may involve the systematic use of currently available longitudinal data, for example, from hospitalised patients or through dedicated software programs utilised by general practitioners.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 103003"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835419","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 : 2026-01-01DOI: 10.1016/j.arr.2025.102998
Hamidreza Khodajou-Masouleh , Sogol Ghanbari
Diapause is an evolutionarily conserved strategy that enables many organisms to survive prolonged exposure to harsh environmental stressors. During this state, organisms drastically reduce their metabolic rate, halt development, and enhance stress tolerance in an energy-efficient manner. Remarkably, many diapausing organisms appear to substantially slow or suspend aging as a result of profound metabolic depression and developmental arrest. Consequently, diapause and aging appear to be programmed in opposite directions, yet both rely on many of the same master regulatory genes and epigenetic modulators. This review explores the molecular mechanisms underlying diapause-induced stress resistance and metabolic suppression, offering critical insights into how dormant biological systems preserve function and delay aging. Manipulating these shared regulatory networks has led to significant extensions in lifespan and improvements in healthspan across various model organisms. Anhydrobiotic species such as Artemia, Caenorhabditis elegans, and tardigrades can nearly suspend aging during dormancy by downregulating metabolic pathways and accumulating protective macromolecules. Notably, the African turquoise killifish, which has adapted to life in ephemeral ponds, can provide a unique platform to study both diapause and aging within a single vertebrate model. Phenotypic plasticity may offer the most compelling evolutionary explanation for resolving the paradox of how the same regulatory network can produce opposite outcomes in diapause and aging. Overall, diapause offers a powerful natural framework for uncovering anti-aging mechanisms and holds great promise for guiding the development of novel interventions to promote longevity and healthy aging.
{"title":"Diapause and aging: Two opposing yet intertwined biological phenomena","authors":"Hamidreza Khodajou-Masouleh , Sogol Ghanbari","doi":"10.1016/j.arr.2025.102998","DOIUrl":"10.1016/j.arr.2025.102998","url":null,"abstract":"<div><div>Diapause is an evolutionarily conserved strategy that enables many organisms to survive prolonged exposure to harsh environmental stressors. During this state, organisms drastically reduce their metabolic rate, halt development, and enhance stress tolerance in an energy-efficient manner. Remarkably, many diapausing organisms appear to substantially slow or suspend aging as a result of profound metabolic depression and developmental arrest. Consequently, diapause and aging appear to be programmed in opposite directions, yet both rely on many of the same master regulatory genes and epigenetic modulators. This review explores the molecular mechanisms underlying diapause-induced stress resistance and metabolic suppression, offering critical insights into how dormant biological systems preserve function and delay aging. Manipulating these shared regulatory networks has led to significant extensions in lifespan and improvements in healthspan across various model organisms. Anhydrobiotic species such as <em>Artemia</em>, <em>Caenorhabditis elegans</em>, and tardigrades can nearly suspend aging during dormancy by downregulating metabolic pathways and accumulating protective macromolecules. Notably, the African turquoise killifish, which has adapted to life in ephemeral ponds, can provide a unique platform to study both diapause and aging within a single vertebrate model. Phenotypic plasticity may offer the most compelling evolutionary explanation for resolving the paradox of how the same regulatory network can produce opposite outcomes in diapause and aging. Overall, diapause offers a powerful natural framework for uncovering anti-aging mechanisms and holds great promise for guiding the development of novel interventions to promote longevity and healthy aging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102998"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783886","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 : 2026-01-01DOI: 10.1016/j.arr.2025.103004
Haiyang Ni , Mingyu Wang , QiZhu Tang
Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, characterized by complex pathological mechanisms involving myocardial metabolic disorders, vascular dysfunction, and uncontrolled inflammation. DEAD-box (DDX) helicases, a large family of RNA helicases within Superfamily 2 (SF2), are increasingly recognized as pivotal regulators of RNA metabolism, including transcription, splicing, translation, and degradation, via their conserved helicase core and variable terminal domains. Beyond maintaining RNA homeostasis, DDX helicases participate in diverse cellular processes such as cell proliferation, immunity, and stress responses, with emerging roles in CVD pathogenesis.
{"title":"The role of DEAD-box helicases in cardiovascular diseases","authors":"Haiyang Ni , Mingyu Wang , QiZhu Tang","doi":"10.1016/j.arr.2025.103004","DOIUrl":"10.1016/j.arr.2025.103004","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, characterized by complex pathological mechanisms involving myocardial metabolic disorders, vascular dysfunction, and uncontrolled inflammation. DEAD-box (DDX) helicases, a large family of RNA helicases within Superfamily 2 (SF2), are increasingly recognized as pivotal regulators of RNA metabolism, including transcription, splicing, translation, and degradation, via their conserved helicase core and variable terminal domains. Beyond maintaining RNA homeostasis, DDX helicases participate in diverse cellular processes such as cell proliferation, immunity, and stress responses, with emerging roles in CVD pathogenesis.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 103004"},"PeriodicalIF":12.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844543","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 : 2025-12-31DOI: 10.1016/j.arr.2025.103008
Andrea Ticinesi , Giovanni Zuliani , Riccardo Spaggiari , Stefano Volpato , Stefania Maggi , Claudio Franceschi
The human gut microbiome (GM) is increasingly recognized as one of the main systems influencing the aging trajectory. Age-related dysbiosis, with imbalance between symbionts and pathobionts, can in fact fuel chronic inflammation (inflammaging) and promote frailty. In older individuals, GM composition is characterized by marked inter-individual variability and consistently influenced by environmental exposures. Studies conducted in animals and closed human communities suggest that social contacts are associated with horizontal transmission of commensal bacteria, enhancing biodiversity and preventing dysbiosis. Recent studies also suggest transmission of intestinal commensal bacteria from animals to humans sharing the same household. Bacterial populations residing on environmental surfaces may also have an influence on GM composition. In this framework, impoverishment of social relationships in older individuals may not be only associated with cognitive and emotional disengagement, but also with unfavorable changes in GM composition, driven by isolation and top-down neuromodulation of intestinal function. In fact, studies conducted during forced social distancing in the COVID-19 pandemic suggest GM changes pointing towards dysbiosis. Therefore, the detrimental consequences of social isolation for health outcomes of older individuals, including frailty progression towards disability, could be at least partly mediated by GM dysbiosis. Conversely, interventions aimed at restoring sociality, including animal-assisted activities, could expose older individuals to a range of novel bacterial species helping to counteract GM dysbiosis. This perspective article critically discusses the concept of social microbiome, its possible relevance for maintenance of good health in human beings, and its implications for the care of older patients.
{"title":"The social microbiome of older people","authors":"Andrea Ticinesi , Giovanni Zuliani , Riccardo Spaggiari , Stefano Volpato , Stefania Maggi , Claudio Franceschi","doi":"10.1016/j.arr.2025.103008","DOIUrl":"10.1016/j.arr.2025.103008","url":null,"abstract":"<div><div>The human gut microbiome (GM) is increasingly recognized as one of the main systems influencing the aging trajectory. Age-related dysbiosis, with imbalance between symbionts and pathobionts, can in fact fuel chronic inflammation (inflammaging) and promote frailty. In older individuals, GM composition is characterized by marked inter-individual variability and consistently influenced by environmental exposures. Studies conducted in animals and closed human communities suggest that social contacts are associated with horizontal transmission of commensal bacteria, enhancing biodiversity and preventing dysbiosis. Recent studies also suggest transmission of intestinal commensal bacteria from animals to humans sharing the same household. Bacterial populations residing on environmental surfaces may also have an influence on GM composition. In this framework, impoverishment of social relationships in older individuals may not be only associated with cognitive and emotional disengagement, but also with unfavorable changes in GM composition, driven by isolation and top-down neuromodulation of intestinal function. In fact, studies conducted during forced social distancing in the COVID-19 pandemic suggest GM changes pointing towards dysbiosis. Therefore, the detrimental consequences of social isolation for health outcomes of older individuals, including frailty progression towards disability, could be at least partly mediated by GM dysbiosis. Conversely, interventions aimed at restoring sociality, including animal-assisted activities, could expose older individuals to a range of novel bacterial species helping to counteract GM dysbiosis. This perspective article critically discusses the concept of social microbiome, its possible relevance for maintenance of good health in human beings, and its implications for the care of older patients.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103008"},"PeriodicalIF":12.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893354","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 : 2025-12-29DOI: 10.1016/j.arr.2025.103006
Tu Chen Guan , Li Zeng , Mei Liu , Yan Liu , Yun-Cheng Wu , Yu Guan Mu , Eng King Tan , Zhi Dong Zhou
RNA G-quadruplexes (rG4s) are stable secondary structures formed by guanine-rich RNA sequences that have emerged as critical regulators of RNA metabolism. The rG4s are widespread in both coding and noncoding RNAs and have been implicated in regulating multiple post-transcriptional processes, including RNA stability, splicing, polyadenylation, nuclear export, localization, and translation. Recent findings reveal that rG4s play pathological roles in neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson’s disease (PD). The rG4s function in stress granule dynamics, aberrant phase separation, and the nucleation of pathological protein assemblies, which is implicated in protein co-aggregation and pathological protein aggregation in NDs. Here, we provide an integrated synthesis of how rG4s influence protein aggregation through biophysical, cellular, and molecular mechanisms, with particular emphasis on rG4-driven perturbations of phase separation and aggregation pathways. The rG4s relevant disease pathogenesis, biomarker development, and therapeutic interventions in NDs are discussed. Furthermore, we highlight emerging translational opportunities, including the potential of rG4-targeting small molecules such as 5-aminolevulinic acid (5-ALA) and other modulators, which may open new avenues for combating neurodegeneration.
RNA g -四重复合物（rG4s）是由富含鸟嘌呤的RNA序列形成的稳定二级结构，已成为RNA代谢的关键调节因子。rG4s广泛存在于编码和非编码RNA中，并参与调控多种转录后过程，包括RNA稳定性、剪接、聚腺苷化、核输出、定位和翻译。最近的研究表明，rG4s在神经退行性疾病（NDs）中发挥病理作用，包括阿尔茨海默病（AD）和帕金森病（PD）。rG4s在应力颗粒动力学、异常相分离和病理蛋白组装成核中起作用，这与NDs中的蛋白共聚集和病理蛋白聚集有关。在这里，我们提供了rG4s如何通过生物物理、细胞和分子机制影响蛋白质聚集的综合合成，特别强调了rg4驱动的相分离和聚集途径的扰动。讨论了NDs中rG4s相关的疾病发病机制、生物标志物的发展和治疗干预措施。此外，我们强调了新兴的转化机会，包括rg4靶向小分子如5-氨基乙酰丙酸和其他调节剂的潜力，这可能为对抗神经变性开辟新的途径。
{"title":"RNA G-quadruplexes mediated protein aggregation in neurodegenerative diseases","authors":"Tu Chen Guan , Li Zeng , Mei Liu , Yan Liu , Yun-Cheng Wu , Yu Guan Mu , Eng King Tan , Zhi Dong Zhou","doi":"10.1016/j.arr.2025.103006","DOIUrl":"10.1016/j.arr.2025.103006","url":null,"abstract":"<div><div>RNA G-quadruplexes (rG4s) are stable secondary structures formed by guanine-rich RNA sequences that have emerged as critical regulators of RNA metabolism. The rG4s are widespread in both coding and noncoding RNAs and have been implicated in regulating multiple post-transcriptional processes, including RNA stability, splicing, polyadenylation, nuclear export, localization, and translation. Recent findings reveal that rG4s play pathological roles in neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson’s disease (PD). The rG4s function in stress granule dynamics, aberrant phase separation, and the nucleation of pathological protein assemblies, which is implicated in protein co-aggregation and pathological protein aggregation in NDs. Here, we provide an integrated synthesis of how rG4s influence protein aggregation through biophysical, cellular, and molecular mechanisms, with particular emphasis on rG4-driven perturbations of phase separation and aggregation pathways. The rG4s relevant disease pathogenesis, biomarker development, and therapeutic interventions in NDs are discussed. Furthermore, we highlight emerging translational opportunities, including the potential of rG4-targeting small molecules such as 5-aminolevulinic acid (5-ALA) and other modulators, which may open new avenues for combating neurodegeneration.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103006"},"PeriodicalIF":12.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879686","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 : 2025-12-29DOI: 10.1016/j.arr.2025.103007
Yanli Han , Weihao Sun , Jian Han , Suxia Li , Yue Zhou
<div><h3>Background</h3><div>Hypertension is a significant risk factor for cardiovascular disease on a global scale, particularly among middle-aged and elderly individuals. Hypertension is not only associated with cardiovascular disease, including heart disease and stroke, but also leads to vascular endothelial dysfunction and decreased cardiac function. Among non-pharmacological intervention modalities, traditional Chinese mind-body exercise therapy can regulate blood pressure, induce psychological relaxation and improve cardiovascular health through gentle exercise with respiratory regulation. However, further verification is required to confirm the specific effects of this therapy.</div></div><div><h3>Methods</h3><div>Relevant randomized controlled trials (RCTs) published after 2000 were searched and screened in Chinese and English databases. A systematic review and frequency network meta-analysis (NMA) were used to assess the effects of six traditional Chinese mind-body exercise therapies, Taichi, Baduanjin, Liuzijue, Shuxinpingxuegong, Qigong, and Daoyinyangshengshu, on blood pressure (systolic blood pressure, diastolic blood pressure), vascular endothelial function secretion factors (nitric oxide, endothelin-1) and cardiac function (heart rate, cardiac output, stroke volume, cardiac index, ejection fraction). The risk of bias was independently assessed using the RoB tool, and the quality of evidence for outcome indicators was evaluated using the Confidence in Network Meta-Analysis (CINeMA) online tool.</div></div><div><h3>Results</h3><div>A total of 48 RCTs (4184 patients) were included in this study, of which 77.6 % were assessed as having a low risk of bias. Of the various exercise interventions, Taichi was the most commonly used, accounting for 51.02 % of cases, while Baduanjin was the second most prevalent, representing 26.53 % of cases. The mean duration of a single exercise session for patients was 48.8 min, with most intervention cycles exceeding 12 weeks and an average frequency of 3.9 sessions per week. The NMA results revealed that Taichi was most effective in reducing systolic blood pressure (SMD = -1.10, 95 % CI [-1.23, -0.98]), improving cardiac output (SMD = 1.31, 95 % CI [0.42, 2.20]), and enhancing cardiac index (SMD = 0.43, 95 % CI [0.02, 0.84]) among middle-aged and elderly patients. Baduanjin exercise was found to be the most effective in reducing heart rate (SMD = -1.60, 95 % CI [-2.01, -1.18]), increasing nitric oxide levels (SMD = 0.96, 95 % CI [0.58, 1.33]), and decreasing endothelin-1 concentrations (SMD = -0.91, 95 % CI [-1.29, −0.52]). Daoyinyangshengshu was the most effective in improving diastolic blood pressure (SMD = -1.26, 95 % CI [-1.65, -0.87]) and elevating stroke volume (SMD = 0.93, 95 % CI [0.47, 1.38]). Liuzijue was the most effective in improving ejection fraction (SMD = 3.30, 95 % CI [1.73, 4.88]).</div></div><div><h3>Conclusion</h3><div>Taichi, Baduanjin and Daoyinyangshengshu are the most suitable ex
{"title":"Effects of six traditional Chinese mind-body exercise therapies on vascular health and cardiac function in middle-aged and elderly hypertensive patients: A network meta-analysis of 48 randomized controlled trials","authors":"Yanli Han , Weihao Sun , Jian Han , Suxia Li , Yue Zhou","doi":"10.1016/j.arr.2025.103007","DOIUrl":"10.1016/j.arr.2025.103007","url":null,"abstract":"<div><h3>Background</h3><div>Hypertension is a significant risk factor for cardiovascular disease on a global scale, particularly among middle-aged and elderly individuals. Hypertension is not only associated with cardiovascular disease, including heart disease and stroke, but also leads to vascular endothelial dysfunction and decreased cardiac function. Among non-pharmacological intervention modalities, traditional Chinese mind-body exercise therapy can regulate blood pressure, induce psychological relaxation and improve cardiovascular health through gentle exercise with respiratory regulation. However, further verification is required to confirm the specific effects of this therapy.</div></div><div><h3>Methods</h3><div>Relevant randomized controlled trials (RCTs) published after 2000 were searched and screened in Chinese and English databases. A systematic review and frequency network meta-analysis (NMA) were used to assess the effects of six traditional Chinese mind-body exercise therapies, Taichi, Baduanjin, Liuzijue, Shuxinpingxuegong, Qigong, and Daoyinyangshengshu, on blood pressure (systolic blood pressure, diastolic blood pressure), vascular endothelial function secretion factors (nitric oxide, endothelin-1) and cardiac function (heart rate, cardiac output, stroke volume, cardiac index, ejection fraction). The risk of bias was independently assessed using the RoB tool, and the quality of evidence for outcome indicators was evaluated using the Confidence in Network Meta-Analysis (CINeMA) online tool.</div></div><div><h3>Results</h3><div>A total of 48 RCTs (4184 patients) were included in this study, of which 77.6 % were assessed as having a low risk of bias. Of the various exercise interventions, Taichi was the most commonly used, accounting for 51.02 % of cases, while Baduanjin was the second most prevalent, representing 26.53 % of cases. The mean duration of a single exercise session for patients was 48.8 min, with most intervention cycles exceeding 12 weeks and an average frequency of 3.9 sessions per week. The NMA results revealed that Taichi was most effective in reducing systolic blood pressure (SMD = -1.10, 95 % CI [-1.23, -0.98]), improving cardiac output (SMD = 1.31, 95 % CI [0.42, 2.20]), and enhancing cardiac index (SMD = 0.43, 95 % CI [0.02, 0.84]) among middle-aged and elderly patients. Baduanjin exercise was found to be the most effective in reducing heart rate (SMD = -1.60, 95 % CI [-2.01, -1.18]), increasing nitric oxide levels (SMD = 0.96, 95 % CI [0.58, 1.33]), and decreasing endothelin-1 concentrations (SMD = -0.91, 95 % CI [-1.29, −0.52]). Daoyinyangshengshu was the most effective in improving diastolic blood pressure (SMD = -1.26, 95 % CI [-1.65, -0.87]) and elevating stroke volume (SMD = 0.93, 95 % CI [0.47, 1.38]). Liuzijue was the most effective in improving ejection fraction (SMD = 3.30, 95 % CI [1.73, 4.88]).</div></div><div><h3>Conclusion</h3><div>Taichi, Baduanjin and Daoyinyangshengshu are the most suitable ex","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103007"},"PeriodicalIF":12.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879657","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 : 2025-12-24DOI: 10.1016/j.arr.2025.103005
Zhenkai Zhang , Haonan Xu , Fuxia Zhao , Zheyue Han , Juan Pan , Mengmeng Li , Wei Guan , Peng Jiang , Zhichao Hao , Yiqiang Zhang , Xiaochi Ma , Haixue Kuang , Yan Liu
Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder, defined pathologically by the accumulation of Aβ plaques and Tau neurofibrillary tangles, accompanied by widespread metabolic dysregulation. Recently, “metabolic reprogramming (MetR)”, referring to the dynamic adaptation of cellular metabolic networks in response to environmental or functional demands, has emerged as a novel conceptual perspective for understanding AD. In the context of AD, the dysregulation of MetR is manifested by widespread disturbances in glucose, lipid, and amino acid metabolism, in addition to mitochondrial impairment. The distinctive therapeutic potential of natural products (NPs) in the management of AD is highlighted by their ability to act synergistically to rebalance disrupted metabolic pathways, owing to their multitarget actions, low toxicity, and broad bioactivity. This review provides a comprehensive overview of the pathological characteristics and molecular basis of “metabolic–mitochondrial” reprogramming in AD and focuses on the potential mechanisms of NPs in this context. Elucidation of these mechanisms is expected to provide novel theoretical foundations and strategic directions for early diagnosis, targeted intervention, and the pharmacological development of NPs–based therapies for AD.
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Pub Date : 2025-12-20DOI: 10.1016/j.arr.2025.102999
Osvaldo Delbono , Zhong-Min Wang, María Laura Messi
<div><div>Neuronal hyperexcitability—defined as increased likelihood of action potential firing in response to stimuli—has emerged as a key pathophysiological feature in both normal aging and Alzheimer’s disease (AD). This review synthesizes current evidence across species and models, evaluating the prevalence, mechanisms, and consequences of heightened excitability at the cellular and network levels. We examine electrophysiological and imaging-based indicators of hyperexcitability, including enhanced spontaneous firing, increased calcium transients, and subclinical epileptiform activity. Data from rodent models and human studies reveal that hyperexcitability arises early in aging and AD, affecting key regions such as the hippocampus, prefrontal cortex, locus coeruleus, and spinal motor circuits. Importantly, this phenomenon is not uniformly pathological: some aged individuals, including so-called “super-agers,” retain stable excitability profiles, suggesting the existence of protective mechanisms. We further explore the functional impact of hyperexcitability, including impaired cognitive encoding, gait disturbances, muscle fatigue, and neuromuscular junction degradation. In the later stages of the disease, neuronal activity tends to shift toward hypoexcitability or shows a deceleration of prior hyperexcitability, primarily driven by progressive synaptic loss, accumulation of tau pathology, and metabolic failure. Current gaps in knowledge include the lack of longitudinal data, limited translation from animal models, and insufficient understanding of compensatory vs. detrimental excitability shifts. Emerging strategies—ranging from pharmacological modulation to neuromodulation and metabolic interventions—offer potential therapeutic avenues. We propose future directions including computational modeling, humanized chimeric models, and excitability biomarkers to guide intervention. Overall, neuronal hyperexcitability represents both a biomarker and modifiable contributor to aging- and AD-related decline. Its study offers a window into early-stage dysfunction and a target for disease-modifying interventions. This review critically examines the emerging evidence for neuronal hyperexcitability as a defining feature of brain aging and AD. We begin by clarifying the concept of hyperexcitability and outlining key cellular and network-level indicators used to detect it. We then synthesize findings on hyperexcitability in aging individuals, both human and animal, and extend this analysis to AD, highlighting overlapping and divergent mechanisms. A focused section explores how motor neuron hyperexcitability contributes to functional decline, followed by a discussion of the transition from early hyperexcitability to late deceleration of neuronal excitability across disease progression. Comparative insights across species and models are provided to underscore translational relevance. We also address current limitations and propose novel investigative directions,
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Pub 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":"2025-12-20","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}
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