Aging and Disease最新文献_第6页

Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases. 视网膜色素上皮吞噬与视网膜退行性疾病。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-25 DOI: 10.14336/AD.2025.0542

Yuxiang Du, Yong Xia

{"title":"Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases.","authors":"Yuxiang Du, Yong Xia","doi":"10.14336/AD.2025.0542","DOIUrl":"https://doi.org/10.14336/AD.2025.0542","url":null,"abstract":"In the mammalian retina, photoreceptors rely on the continuous renewal of their outer segments to preserve their function as light-sensing cells, thereby ensuring lifelong vision. This process entails the routine phagocytosis of shed photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE). Phagocytosis of POS by RPE is a highly circadian-regulated process that is dependent on intricate and tightly controlled cellular signaling pathways. This article provides a systematic review of the research on the regulation and functional implications of the RPE phagocytic signaling system. Therefore, a deeper understanding of the role of retinal pigment epithelial phagocytosis in the pathogenesis of retinal degeneration can inform the development of potential therapeutic targets to prevent the irreversible loss of retinal pigment epithelium and photoreceptor cells, thereby preventing retinal degenerative diseases. This article summarizes the soluble and membrane-bound molecules produced by the RPE that are associated with phagocytosis and discusses their specific roles in POS phagocytosis and retinal degenerative disorders, potentially aiding in the prevention or treatment of retinal degenerative diseases.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease. 葡萄糖代谢，乳酸，乳酸化和阿尔茨海默病。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-25 DOI: 10.14336/AD.2025.0338

Shuangshuang Hai, Yadan Hou, Meiyan Zhang, Xiaoyan Gao, Tuo Yang, Xiuli Shang, Xiaohong Sun

{"title":"Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease.","authors":"Shuangshuang Hai, Yadan Hou, Meiyan Zhang, Xiaoyan Gao, Tuo Yang, Xiuli Shang, Xiaohong Sun","doi":"10.14336/AD.2025.0338","DOIUrl":"https://doi.org/10.14336/AD.2025.0338","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline; however, its pathogenesis remains incompletely understood. In recent years, the role of lactate metabolism and its derived lactylation modifications in AD has received increasing attention. As a product of glycolysis, lactate is not only a key molecule in energy metabolism but also regulates gene expression and protein function through lactylation modifications. Studies have shown that in the brains of AD patients, glucose metabolism is significantly reduced, while glycolysis is upregulated, and lactate levels are elevated. Nevertheless, the research regarding the relationship between lactylation and AD remains limited. Building on recent advances in understanding lactylation in neurodegenerative diseases and related conditions, we analyze and explore the potential relationships between lactylation and AD from the perspectives of β-amyloid (Aβ) deposition, tau protein pathology, and neuroinflammation. In summary, lactylation, as a novel post-translational modification holds significant promise in elucidating the pathological mechanisms and advancing the treatment of AD. A deeper investigation into its molecular mechanisms and regulatory networks may open new avenues for the diagnosis and treatment of AD.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Resveratrol: Harnessing Nature's Potential for Chronic Pain Relief. 白藜芦醇：利用自然的潜力缓解慢性疼痛。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-23 DOI: 10.14336/AD.2025.0530

Hong Wu, Jia-Yi Wu, Shao-Jie Gao, Lin Liu, Xin-Yi Dai, Wen-Lu Song, Long-Qing Zhang, Dai-Qiang Liu, Ying-Xin Tang, Ya-Qun Zhou, Wei Mei

引用次数: 0

Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy. 脑卒中加重脑淀粉样血管病小鼠的呼吸障碍和认知障碍。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-23 DOI: 10.14336/AD.2025.0474

YuXing Zhang, Ahmad El Hamamy, Zahid Iqbal, Arya Ranjan, Destiny Sumani, Hung Wen Lin, Louise D McCullough, Jun Li

{"title":"Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy.","authors":"YuXing Zhang, Ahmad El Hamamy, Zahid Iqbal, Arya Ranjan, Destiny Sumani, Hung Wen Lin, Louise D McCullough, Jun Li","doi":"10.14336/AD.2025.0474","DOIUrl":"https://doi.org/10.14336/AD.2025.0474","url":null,"abstract":"Stroke is a known risk factor for dementia. Most Alzheimer's patients exhibit mixed neuropathology, with evidence of both ischemic damage and amyloid-beta (Aβ) plaque accumulation. Breathing disorders, such as apnea, are also associated with cognitive dysfunction and dementia progression. We hypothesized that stroke exacerbates respiratory dysfunction and cognitive impairment in Tg-SwDI mice, a model of cerebral amyloid angiopathy (CAA). Female CAA mice (11-13 months old) underwent permanent distal middle cerebral artery occlusion (pd-MCAO) surgery, with age- and sex-matched wild-type and sham-operated controls. Cognitive assessments included the Barnes maze, and novel object recognition test (NORT). Respiratory metrics were quantified using whole-body plethysmography, while immunohistochemistry measured Aβ deposition in the hippocampus and cortex, astrocytic markers (C3⁺GFAP⁺ for A1; S100A10⁺GFAP⁺ for A2) in the retrotrapezoid nucleus (RTN), and lymphatic vessel area (LYVE1) in deep cervical lymph nodes (dCLNs). Aβ in cerebrospinal fluid was also assessed. CAA mice without stroke exhibited higher apnea rates and impaired cognitive performance compared to wild-type controls. Stroke further increased apnea events and worsened Barnes maze escape latencies in CAA mice. Molecular analysis revealed an increase in GFAP as well as in A1 astrocytes and a reduction in A2 astrocytes in the RTN following stroke. Additionally, stroke accelerated Aβ deposition in the hippocampus and cortex while reducing Aβ clearance via cerebrospinal fluid and dCLNs. These findings suggest that stroke exacerbates respiratory dysfunction, impairs glymphatic-lymphatic clearance, and accelerates cognitive decline in CAA mice. Targeting post-stroke respiratory dysfunction may offer therapeutic potential for mitigating ischemic damage in dementia patients.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism. 帕金森病代谢失调：非氧化磷酸化及其在脑能量代谢中的作用

IF 6.9 2区医学

Aging and Disease Pub Date : 2025-06-22 DOI: 10.14336/AD.2025.0619

Marta Pokotylo, Norbert Brüggemann, Jannik Prasuhn

{"title":"Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.","authors":"Marta Pokotylo, Norbert Brüggemann, Jannik Prasuhn","doi":"10.14336/AD.2025.0619","DOIUrl":"10.14336/AD.2025.0619","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurodegenerative condition affecting around 1-2% of the population over the age of 60. The lack of disease-modifying therapies highlights the need for insights into the etiology and pathogenesis of PD. Mitochondrial dysfunction is recognized to be a significant contributor to disease pathogenesis, resulting in bioenergetic deficits and subsequent neurodegeneration. Research indicates that changes in non-oxidative phosphorylation (non-OXPHOS) metabolism in PD may serve as an adaptive response to mitochondrial dysfunction, compensating for energetic failure and alleviating disease progression. This review explores mitochondrial dysfunction-driven alterations in non-OXPHOS metabolic pathways, such as glycolysis and the tricarboxylic acid cycle, emphasizing their role in maintaining energy metabolism and their dual contribution to neuroprotection and disease progression. Advances in neuroimaging techniques are also discussed, particularly their role in visualizing metabolic changes in vivo and their potential utility in identifying non-OXPHOS metabolism as a biomarker of mitochondrial dysfunction. By enhancing our understanding of the complex interplay between metabolic pathways in PD, this review underscores the importance of personalized therapeutic approaches that consider individual metabolic variations. Ultimately, these insights aim to pave the way for improved diagnostic utility and personalized treatment strategies that address the metabolic and mitochondrial dysfunctions underlying PD pathogenesis.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":"2721-2738"},"PeriodicalIF":6.9,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exercise-Induced Short-Chain Fatty Acids: A Novel Therapeutic Target in Type 2 Diabetes Mellitus with Sarcopenia. 运动诱导的短链脂肪酸：2型糖尿病伴肌少症的新治疗靶点。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-20 DOI: 10.14336/AD.2025.0670

Fan Shi, Jun Chen

{"title":"Exercise-Induced Short-Chain Fatty Acids: A Novel Therapeutic Target in Type 2 Diabetes Mellitus with Sarcopenia.","authors":"Fan Shi, Jun Chen","doi":"10.14336/AD.2025.0670","DOIUrl":"https://doi.org/10.14336/AD.2025.0670","url":null,"abstract":"Type 2 diabetes mellitus accompanied by sarcopenia is an emerging clinical challenge in aging populations, characterized by coexisting metabolic dysfunction and the progressive loss of skeletal muscle mass and function. This comorbidity substantially elevates the risk of frailty, functional impairment, and poor clinical outcomes, highlighting the urgent need for targeted therapeutic interventions. Growing evidence suggests that gut microbiota dysbiosis contributes to the pathogenesis of both Type 2 diabetes mellitus and sarcopenia through mechanisms such as chronic inflammation, insulin resistance, and mitochondrial and autophagic dysfunction. Among gut-derived metabolites, short-chain fatty acids exert anti-inflammatory and insulin-sensitizing effects and also promote muscle metabolism and mitochondrial function. Notably, exercise increases the abundance of short-chain fatty acid-producing bacteria, thereby elevating circulating short-chain fatty acid levels and contributing to improved glucose homeostasis and skeletal muscle function. This review summarizes the effects of various exercise modalities on short-chain fatty acid production and explores the mechanisms by which short-chain fatty acids mediate the benefits of exercise in Type 2 diabetes mellitus complicated by sarcopenia, emphasizing their potential as novel therapeutic targets for integrated disease management.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytic Glucose Sensing Drives Synaptic Depression under Metabolic Stress. 代谢应激下星形细胞葡萄糖感知驱动突触抑制。

IF 6.9 2区医学

Aging and Disease Pub Date : 2025-06-19 DOI: 10.14336/AD.2025.0507

Andrés M Baraibar, Carlos G Ardanaz, Susana Mato, Paulo Kofuji, Alfonso Araque, Maite Solas

{"title":"Astrocytic Glucose Sensing Drives Synaptic Depression under Metabolic Stress.","authors":"Andrés M Baraibar, Carlos G Ardanaz, Susana Mato, Paulo Kofuji, Alfonso Araque, Maite Solas","doi":"10.14336/AD.2025.0507","DOIUrl":"10.14336/AD.2025.0507","url":null,"abstract":"Glucose is the primary energy source for the brain, and its continuous supply is essential for neuronal function. Astrocytes play a pivotal role in brain energy metabolism by mediating glucose uptake, sensing metabolic fluctuations, and modulating synaptic activity. However, astrocyte responses to transient glucose deprivation remain incompletely understood. Here, we demonstrate that astrocytic glucose uptake is crucial for network adaptation to metabolic stress. Using electrophysiology and calcium imaging approaches, we show that glucose deprivation depresses hippocampal synaptic transmission through an astrocyte-dependent mechanism that involves decreased glucose transporter 1 (GLUT1)-facilitated extracellular glucose uptake, intracellular calcium elevations, and ATP/adenosine-mediated signaling, which leads to excitatory neurotransmission depression via A1 receptors. Moreover, astrocyte-specific GLUT1 depletion prevents astrocytic responses to glucose deprivation and precludes the effects of glucose deprivation on synaptic transmission, thereby indicating that GLUT1-dependent glucose uptake is involved in astrocyte-mediated modulation of synaptic function. These findings extend the concept of astrocytic metabolic regulation beyond regions canonically classified as glucose-sensing and establish astrocytes as key integrators of energy availability and synaptic function. Our study provides new insights into the role of astrocytes in brain energy homeostasis and identifies potential therapeutic targets for metabolic disorders affecting the nervous system.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic CTA-Based Whole-Brain Arterial-Venous Collateral Assessment for Predicting Futile Recanalization in Acute Ischemic Stroke. 基于动态cta的全脑动静脉侧支评估预测急性缺血性卒中无效再通。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-19 DOI: 10.14336/AD.2025.0540

Ruoyao Cao, Yao Lu, Wei Li, Fan Yu, Shen Hu, Kunpeng Chen, Guoxuan Wang, Chengkan Sun, Qingfeng Ma, Miao Zhang, Juan Chen, Jie Lu

{"title":"Dynamic CTA-Based Whole-Brain Arterial-Venous Collateral Assessment for Predicting Futile Recanalization in Acute Ischemic Stroke.","authors":"Ruoyao Cao, Yao Lu, Wei Li, Fan Yu, Shen Hu, Kunpeng Chen, Guoxuan Wang, Chengkan Sun, Qingfeng Ma, Miao Zhang, Juan Chen, Jie Lu","doi":"10.14336/AD.2025.0540","DOIUrl":"https://doi.org/10.14336/AD.2025.0540","url":null,"abstract":"Futile recanalization is a recognized challenge in acute ischemic stroke (AIS) patients after endovascular treatment (EVT). Our purpose was to develop and validate a predictive model for futile recanalization after EVT by integrating arterial-venous collateral assessment with clinical parameters. This study included 392 AIS patients with acute anterior circulation large vessel occlusion who underwent EVT (March 2016-June 2024). Patients were stratified into training (n = 160), internal validation (n = 69), and completely independent external validation (n = 163) cohorts collected from a separate medical center. Predictors were identified using Boruta algorithm and LASSO regression. Multiple machine learning models were evaluated through discrimination, calibration, and decision curve analyses, with SHAP analysis for feature importance. Three independent predictors were identified: age (OR: 1.06, 95% CI: 1.02-1.11), whole-brain arterial collateral status (OR: 0.30, 95% CI: 0.18-0.50), and whole-brain venous collateral status (OR: 0.78, 95% CI: 0.67-0.90). The model demonstrated excellent discrimination in the training cohort (AUC: 0.914, 95% CI: 0.866-0.963), internal validation cohort (AUC: 0.918, 95% CI: 0.844-0.991), and notably maintained robust performance in the completely independent external validation cohort (AUC: 0.755, 95% CI: 0.678-0.832). Calibration plots showed good agreement between predicted and observed outcomes. SHAP analysis further confirmed the importance of arterial and venous collateral status assessments. The integration of whole-brain arterial-venous collateral assessment with clinical parameters shows potential value in predicting futile recanalization after EVT. This model, validated across multiple cohorts, may provide additional information to support clinical decision-making.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Updates in Intravenous Thrombolysis Treatment for Acute Ischemic Stroke in Asian Populations. 亚洲人群急性缺血性卒中静脉溶栓治疗的最新进展。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-17 DOI: 10.14336/AD.2025.0060

Rui Xue, Anni Wang, Ying Zhou, Min Lou

引用次数: 0

Effective Therapeutic Strategies to Prevent Frailty and Falls in Community-Dwelling Older Adults. 预防社区居住老年人虚弱和跌倒的有效治疗策略。

IF 7 2区医学

Aging and Disease Pub Date : 2025-06-17 DOI: 10.14336/AD.2025.0445

Dmitry Tsvetkov, Marleen J Meyer-Tönnies, Mladen V Tzvetkov, Werner Weitschies, Stefan Engeli, Anna Lebedeva, Anke Hannemann, Martin C Jordan, Ulrike Garscha, Luzia Valentini, Daria Antonenko, Lieven N Kennes, Maik Gollasch

{"title":"Effective Therapeutic Strategies to Prevent Frailty and Falls in Community-Dwelling Older Adults.","authors":"Dmitry Tsvetkov, Marleen J Meyer-Tönnies, Mladen V Tzvetkov, Werner Weitschies, Stefan Engeli, Anna Lebedeva, Anke Hannemann, Martin C Jordan, Ulrike Garscha, Luzia Valentini, Daria Antonenko, Lieven N Kennes, Maik Gollasch","doi":"10.14336/AD.2025.0445","DOIUrl":"10.14336/AD.2025.0445","url":null,"abstract":"Frailty and the consequent risk of falls represent significant challenges for community-dwelling older adults, often leading to severe injuries, functional decline, and loss of independence. Falls typically result from multiple interacting risk factors, many of which are modifiable through targeted interventions. This mini-review focuses on evidence from randomized controlled trials evaluating effective therapeutic strategies to prevent frailty and falls. Comprehensive assessment and management of modifiable risk factors have been shown to significantly reduce fall incidence. Key interventions include community-based and home-based exercise programs emphasizing balance and strength training. Additionally, the treatment of osteoporosis is crucial to reducing the risk of fall-related fractures. Other modifiable risk factors, such as orthostatic hypotension, polypharmacy, environmental hazards, osteoporosis, malnutrition, and cognitive impairment, require targeted assessment and intervention. Despite these advances, further research is needed to optimize multifactorial interventions and tailor strategies to individual risk profiles. Innovative research directions now span from micro to macro levels, incorporating insights from animal models to human studies, aiming to unravel underlying mechanisms and develop personalized therapeutic strategies. This review discusses emerging evidence and new interdisciplinary research avenues that offer hope for mitigating frailty and preventing falls in community-dwelling older adults.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0