Ageing research reviews最新文献

Lipid Dysregulation as a Central Contributor of Neurodegenerative Diseases: Emerging Therapeutic Targets and Strategies. 脂质失调是神经退行性疾病的核心因素：新兴的治疗靶点和策略。

IF 12.4

Ageing research reviews Pub Date : 2026-05-06 DOI: 10.1016/j.arr.2026.103159

Jiajie Zhang, Chenzhi Wang, Yanan Li, Zemeng Xiao, Zhenzhen Cai, Yuxuan Qian, Lei Shi, Qi Zhang

{"title":"Lipid Dysregulation as a Central Contributor of Neurodegenerative Diseases: Emerging Therapeutic Targets and Strategies.","authors":"Jiajie Zhang, Chenzhi Wang, Yanan Li, Zemeng Xiao, Zhenzhen Cai, Yuxuan Qian, Lei Shi, Qi Zhang","doi":"10.1016/j.arr.2026.103159","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103159","url":null,"abstract":"Lipid homeostasis is essential for preserving the structural integrity and functional capacity of the brain. A diverse array of lipids, including cholesterol, phospholipids, and sphingolipids, has been identified as playing pivotal roles. Dysregulation of lipid metabolism is increasingly recognized as a central pathological mechanism in neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Cerebrotendinous Xanthomatosis, though much of the existing evidence comes from associative studies, and causal relationships still need to be further validated through interventional studies. Here we systematically review the metabolic pathways and regulatory networks of major brain lipids, with a focus on delineating disease-specific alterations and summarizing emerging therapeutic strategies targeting lipid metabolism. These strategies encompass the modulation of cholesterol homeostasis, sphingolipid metabolism, phospholipid signaling, and fatty acid oxidation, alongside approaches that enhance lipid clearance and neural repair. Preclinical advances and ongoing clinical trials underscore the translational potential of lipid-targeted interventions. In conclusion, we emphasize the potential of lipid metabolism as a promising avenue for developing novel treatments, offering insights to guide future research and therapeutic innovation in neurodegeneration.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103159"},"PeriodicalIF":12.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Neurogenesis in Neurodegenerative Diseases: Mechanisms and Interventions. 神经发生在神经退行性疾病中的作用：机制和干预措施。

IF 12.4

Ageing research reviews Pub Date : 2026-05-05 DOI: 10.1016/j.arr.2026.103160

Ruiqi Chen, Zixiong Qiu, Yao Luo, Yuan Fu, Xiaojun Cui, Mei Jiang

引用次数: 0

Nitric oxide redox signaling as a convergent mechanism in aging and fibrosis. 一氧化氮氧化还原信号在衰老和纤维化中的趋同机制。

IF 12.4

Ageing research reviews Pub Date : 2026-05-01 DOI: 10.1016/j.arr.2026.103156

Xue Guo, Yubin Cao, Liu Liu, Yangqing Peng, Yu Du, Fan Yang, Dingming Huang

{"title":"Nitric oxide redox signaling as a convergent mechanism in aging and fibrosis.","authors":"Xue Guo, Yubin Cao, Liu Liu, Yangqing Peng, Yu Du, Fan Yang, Dingming Huang","doi":"10.1016/j.arr.2026.103156","DOIUrl":"10.1016/j.arr.2026.103156","url":null,"abstract":"Nitric oxide (NO) is a pleiotropic gaseous mediator that regulates tissue homeostasis. At physiological levels, it functions as a precise signaling molecule through soluble guanylate cyclase (sGC) activation and the reversible S-nitrosylation of cysteine residues. However, in the context of aging and fibrosis, oxidative stress disrupts this balance. The increased generation of superoxide (O₂•⁻) anions diverts NO from homeostatic signaling to form peroxynitrite (ONOO⁻), a potent oxidant. This biochemical transition drives cellular dysfunction by promoting the senescence-associated secretory phenotype (SASP), dysregulating nutrient sensing pathways including the PI3K-Akt-PTEN and AMPK-mTOR, and disrupting proteostasis. Moreover, this redox dysregulation perpetuates fibrosis by inducing myofibroblast differentiation and altering extracellular matrix stability via matrix metalloproteinases. This review delineates the NO-redox axis as a convergent mechanism linking the aging-fibrosis synergy. It highlights how the shift from protective S-nitrosylation to pathological protein nitration locks tissues in a dysfunctional state. Finally, therapeutic strategies targeting this axis are explored, emphasizing the limitations of non-selective antioxidants. Consequently, emphasis is placed on precision redox pharmacology approaches that integrate selective peroxynitrite scavengers and endothelial nitric oxide synthase recoupling agents with metabolic modulators including glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. This framework provides new perspectives for the development of targeted interventions against aging-related fibrotic diseases.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103156"},"PeriodicalIF":12.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory mechanisms of age-related degenerative diseases: Insights from the gut microbiota-cellular senescence interaction network. 年龄相关退行性疾病的调节机制：来自肠道微生物群-细胞衰老相互作用网络的见解。

IF 12.4

Ageing research reviews Pub Date : 2026-04-29 DOI: 10.1016/j.arr.2026.103152

Peng Sun, Guannan Chen, Yilan Guo

{"title":"Regulatory mechanisms of age-related degenerative diseases: Insights from the gut microbiota-cellular senescence interaction network.","authors":"Peng Sun, Guannan Chen, Yilan Guo","doi":"10.1016/j.arr.2026.103152","DOIUrl":"10.1016/j.arr.2026.103152","url":null,"abstract":"Global population aging has sharply increased the prevalence of age-related degenerative diseases, posing severe challenges to global public health and socioeconomic stability. Growing evidence links these disorders to the bidirectional crosstalk between gut microbiota and cellular senescence, yet the integrated interaction network governing multi-organ degeneration remains poorly defined. Age-related gut microbial remodeling reshapes metabolite profiles: beneficial metabolites mitigate cellular senescence through epigenetic regulation, antioxidant defense, inflammatory signaling inhibition, intestinal barrier maintenance and immune modulation, while detrimental metabolites induce cellular senescence via inflammatory cascade activation, mitochondrial dysfunction, DNA damage, endoplasmic reticulum stress and intestinal barrier impairment. The intestinal barrier-immune axis mediates the systemic propagation of senescence signals, and senescent cells together with their senescence-associated secretory phenotype (SASP) further exacerbate gut microbial dysbiosis to form a pathological vicious cycle. This review systematically dissects this interaction network and its pathogenic role in major degenerative diseases, and highlights precision targeting of this network as a promising strategy to intervene in these intractable diseases.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103152"},"PeriodicalIF":12.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apolipoprotein E4 and synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic implications. 载脂蛋白E4与阿尔茨海默病的突触功能障碍：机制和治疗意义。

IF 12.4

Ageing research reviews Pub Date : 2026-04-28 DOI: 10.1016/j.arr.2026.103153

Zhiying Yao, Ivan Steve Godje Godje, Bin Jiao, Lu Shen, Shilin Luo

{"title":"Apolipoprotein E4 and synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic implications.","authors":"Zhiying Yao, Ivan Steve Godje Godje, Bin Jiao, Lu Shen, Shilin Luo","doi":"10.1016/j.arr.2026.103153","DOIUrl":"10.1016/j.arr.2026.103153","url":null,"abstract":"Alzheimer's disease (AD) is characterized by progressive cognitive decline, with synaptic dysfunction as the strongest correlate of clinical symptoms. The apolipoprotein E ε4 (ApoE4) allele is the most potent genetic risk factor for late-onset AD. Beyond its roles in amyloid-β aggregation and tau hyperphosphorylation, ApoE4 disrupts synaptic integrity by perturbing lipid metabolism, neuroimmune regulation, mitochondrial dynamics, and activity-dependent plasticity. These ApoE4-driven mechanisms impair presynaptic vesicle trafficking, destabilize postsynaptic receptor and scaffolding networks (including PSD-95, SynGAP, and Shank3), and accelerate complement- and microglia-mediated synaptic pruning. Collectively, these processes converge to destabilize neuronal circuits and drive early cognitive decline. In this review, we synthesize current evidence on the molecular mechanisms by which ApoE4 compromises synaptic function, with particular emphasis on lipid microdomain instability, mitochondrial failure, and the collapse of postsynaptic density proteins. We also discuss therapeutic strategies to enhance synaptic resilience, including modulation of glutamatergic transmission, restoration of lipid homeostasis, augmentation of neurotrophic signaling, and regulation of microglial activity. Targeting synaptic preservation in APOE ε4 carriers holds promise as a disease-modifying approach to mitigate cognitive decline in AD.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103153"},"PeriodicalIF":12.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction notice to "Prevention of cardiovascular disease for healthy aging and longevity: A new scoring system and related "mechanisms-hallmarks-biomarkers"" [Ageing Research Reviews 107 (2025) 102727]. 《预防心血管疾病促进健康老龄化和长寿：一种新的评分系统及相关“机制-标志-生物标志物”》[老龄化研究综述107(2025)102727]。

IF 12.4

Ageing research reviews Pub Date : 2026-04-15 DOI: 10.1016/j.arr.2026.103130

Chunsong Hu

引用次数: 0

Hallmarks of healthy cognitive aging: inter-individual differences in aging trajectories. 健康认知衰老的标志：衰老轨迹的个体间差异。

IF 12.4

Ageing research reviews Pub Date : 2026-03-20 DOI: 10.1016/j.arr.2026.103102

Djoher Nora Abrous, Nicolas Blin, Carl-Johan Boraxbekk, Gwenaelle Catheline, Carlos P Fitzsimons, Markus Hilscher, Maël Lemoine, Luísa V Lopes, Anne Maass, Mats Nilsson, Lars Nyberg, Lene Juel Rassmussen, Miguel Remondes, Magdalena Sauvage, Stefanie Schreiber, Thomas Wolbers

{"title":"Hallmarks of healthy cognitive aging: inter-individual differences in aging trajectories.","authors":"Djoher Nora Abrous, Nicolas Blin, Carl-Johan Boraxbekk, Gwenaelle Catheline, Carlos P Fitzsimons, Markus Hilscher, Maël Lemoine, Luísa V Lopes, Anne Maass, Mats Nilsson, Lars Nyberg, Lene Juel Rassmussen, Miguel Remondes, Magdalena Sauvage, Stefanie Schreiber, Thomas Wolbers","doi":"10.1016/j.arr.2026.103102","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103102","url":null,"abstract":"Cognitive aging is a highly heterogeneous process, with some individuals preserving stable cognitive performance across the lifespan while others exhibiting pronounced decline. This marked interindividual variability indicates that chronological age alone is a poor predictor of cognitive health. Rather than reflecting uniform degeneration, cognitive aging emerges from divergent biological trajectories spanning molecular, cellular, and network levels. In this review, we synthesize emerging biological hallmarks of healthy cognitive aging, emphasizing studies that characterize longitudinal cognitive trajectories in humans or distinguish aged individuals who retain learning capacity from those who do not. We focus on the medial temporal lobe, a region critical for episodic memory and spatial navigation, and examine how variability in its integrity contributes to distinct cognitive outcomes. Across species, convergent evidence suggests that cognitive decline is more closely linked to alterations in network regulation and synaptic plasticity than to overt neuronal loss. We identify key mechanisms shaping individual trajectories, including large-scale network organization, excitation-inhibition balance, neuromodulatory tone, glial and vascular regulation, adult hippocampal neurogenesis, and cellular homeostasis. These processes operate within an interconnected system in which disruptions in core regulatory mechanisms can propagate across levels of organization. Together, this synthesis supports a system-level framework in which cognitive resilience depends on the preservation of coordinated network dynamics. We advocate for longitudinal, multidimensional approaches to identify early shifts in regulatory balance and inform strategies to maintain cognitive function across the lifespan.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103102"},"PeriodicalIF":12.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactylation and methylation: Dual epigenetic codes and potential therapeutic targets in myocardial aging. 乳酸化和甲基化：心肌老化的双重表观遗传密码和潜在治疗靶点。

IF 12.4

Ageing research reviews Pub Date : 2025-12-01 Epub Date: 2025-07-30 DOI: 10.1016/j.arr.2025.102849

Qian-Qian Niu, Yu-Ting Xi, Ya-Qi Guo, Zheng-Ji Piao, Chun-Rui Zhang, Tian-Yao Li, Dan-Jie Li, Peng Li, Ya-Ling Yin, Vuanghao Lim, Nik Nur Syazni Nik Mohamed Kamal

{"title":"Lactylation and methylation: Dual epigenetic codes and potential therapeutic targets in myocardial aging.","authors":"Qian-Qian Niu, Yu-Ting Xi, Ya-Qi Guo, Zheng-Ji Piao, Chun-Rui Zhang, Tian-Yao Li, Dan-Jie Li, Peng Li, Ya-Ling Yin, Vuanghao Lim, Nik Nur Syazni Nik Mohamed Kamal","doi":"10.1016/j.arr.2025.102849","DOIUrl":"10.1016/j.arr.2025.102849","url":null,"abstract":"Combating aging has become a central challenge in the life sciences, and myocardial aging, as a fundamental pathological process underlying the development and progression of various cardiovascular diseases, has become a key area in anti-aging research. In recent years, lactylation and methylation, two metabolism-dependent epigenetic modifications, have garnered increasing attention in the context of myocardial aging. Lactylation, mediated by lactate accumulation due to metabolic dysregulation, modifies lysine residues on both histone and non-histone proteins, thereby participating in the regulation of gene transcription, metabolic homeostasis, and inflammatory responses. In parallel, methylation affects gene expression, metabolic remodeling, and mitochondrial function through DNA, RNA, and histone modifications. This review systematically summarizes the regulatory mechanisms of lactylation and methylation in myocardial aging, with a particular focus on their interplay in histone and non-histone protein modification, metabolic regulation, and signaling pathway integration. Furthermore, we evaluate the potential of these reversible modifications as early epigenetic biomarkers and discuss multilayered intervention strategies targeting both lactylation and methylation. Such strategies highlight their translational potential in delaying myocardial aging and mitigating cardiovascular disease. Precisely modulating lactylation and methylation may offer novel theoretical frameworks and therapeutic targets for the prevention and treatment of myocardial aging.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102849"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of antidiabetic medications on the relationship between type 2 diabetes mellitus and cognitive impairment. 降糖药物对2型糖尿病与认知功能障碍关系的影响。

IF 12.4

Ageing research reviews Pub Date : 2025-12-01 Epub Date: 2025-07-12 DOI: 10.1016/j.arr.2025.102834

Annalisa Cozza, Chiara Chinigò, Elvira Filicetti, Giada Ida Greco, Rosamaria Lappano, Cinzia Marinaro, Lucia Muglia, Luca Soraci, Andrea Corsonello, Fabrizia Lattanzio, Mara Volpentesta

{"title":"Effects of antidiabetic medications on the relationship between type 2 diabetes mellitus and cognitive impairment.","authors":"Annalisa Cozza, Chiara Chinigò, Elvira Filicetti, Giada Ida Greco, Rosamaria Lappano, Cinzia Marinaro, Lucia Muglia, Luca Soraci, Andrea Corsonello, Fabrizia Lattanzio, Mara Volpentesta","doi":"10.1016/j.arr.2025.102834","DOIUrl":"10.1016/j.arr.2025.102834","url":null,"abstract":"Type 2 diabetes mellitus (T2DM)-related cognitive impairment (CI) has garnered increasing attention in recent research and is emerging as a highly relevant area of study. T2DM is a chronic and globally prevalent condition characterized by insulin resistance, hyperglycemia, oxidative stress, neuroinflammation, and cerebrovascular dysfunction, factors that collectively contribute to cognitive decline. Notably, T2DM is strongly associated with neurodegenerative conditions, ranging from mild cognitive impairment (MCI) to dementia. This review explores the potential neuroprotective effects of various antidiabetic drugs, including insulin-sensitizing agents (metformin and pioglitazone), sodium-glucose co-transporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). These medications exert their effects through multiple mechanisms, such as reducing neuroinflammation and oxidative stress, decreasing Aβ accumulation and apoptosis, enhancing cerebral glucose metabolism, and promoting neuroplasticity, processes directly implicated in the interplay between T2DM and cognitive decline. The review highlights the therapeutic potential of these agents in mitigating CI and supporting brain health in individuals with T2DM. However, given the conflicting nature of current clinical evidence, further research is needed to clarify their cognitive benefits, elucidate underlying mechanisms of action, and assess their long-term effects on cognitive outcomes in this population.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102834"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telomerase dynamics in stem cells: Unraveling the molecular nexus of cellular aging and regeneration. 干细胞中的端粒酶动力学：揭示细胞衰老和再生的分子联系。

IF 12.4

Ageing research reviews Pub Date : 2025-12-01 Epub Date: 2025-08-05 DOI: 10.1016/j.arr.2025.102853

Yanhua Jiang, Yongjian Zhou, Yutao Wang, Zhe Li, Ghulam Md Ashraf, Liang Guo

{"title":"Telomerase dynamics in stem cells: Unraveling the molecular nexus of cellular aging and regeneration.","authors":"Yanhua Jiang, Yongjian Zhou, Yutao Wang, Zhe Li, Ghulam Md Ashraf, Liang Guo","doi":"10.1016/j.arr.2025.102853","DOIUrl":"10.1016/j.arr.2025.102853","url":null,"abstract":"The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in the terminally differentiated cells. Minimal telomerase activity is present in the stem and progenitor cells of highly proliferative tissues, although preventing telomere shortening is beyond common sense in the field of biology and cannot be achieved, eventually leading to replicative senescence. While telomerase silencing in somatic cells and adult stem cells acts as a barrier to tumorigenesis by limiting their lifespan, the eventual exhaustion of stem cell pools leads to tissue dysfunction and aging. Telomerase reactivation via telomerase overexpression represents a potential strategy to reverse stem cell aging and rejuvenate aged or dysfunctional tissues. In this review, we discuss the dynamics of telomere (length, activity, and expression level) in pluripotent and adult stem cells as well as their impact on aging. Notably, we have summarized the recent evidence in the application of mesenchymal stem cells immortalized through exogenous telomerase expression in regenerative medicine.","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102853"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0