Aging and Disease最新文献

{"title":"Advanced Age Worsens Phenotypes of Ocular Hypertension in Mice.","authors":"Priyamvada M Pitale, Solomon E Gibson, Caroline C Keehn, Arman T Yazdian, Guofu Shen, Benjamin J Frankfort","doi":"10.14336/AD.2025.0349","DOIUrl":"10.14336/AD.2025.0349","url":null,"abstract":"<p><p>Glaucoma is a neurodegenerative disorder of the optic nerve and retinal ganglion cells (RGCs) and a major cause of blindness. The two most important risk factors for glaucoma are ocular hypertension (OHT) and advanced age. In this study, we explored the combined impact of aging and OHT on retinal neuronal and microvasculature health. We induced OHT using the bead-injection model in 12 week old (young) and 1.5 year old (old) mice and monitored intraocular pressure (IOP) for 2 weeks. We then explored vascular phenotypes, blood retinal barrier components, RGC counts, and electroretinogram (ERG) changes. Aged mice displayed reduced retinal microvasculature complexity, retinal vascular phenotypes in all three retinal capillary plexi (RCPs), and abnormal ERGs. Aging also impacted basement membrane (BM) and tight junction (TJ) morphology. The impact of OHT was much more evident in old mice; RGC loss was exacerbated, retinal vascular phenotypes were magnified across all three RCPs, and BM and TJ phenotypes were much more severe. However, the impact of OHT on retinal function was unchanged in old mice. Interestingly, the nature of these phenotypes was not equivalent among all RCPs, suggesting regional shared and distinct susceptibilities to aging and OHT. Taken together, aging causes multiple neurovascular phenotypes in mouse retinas, and OHT causes more severe effects in old mice. This suggests an interaction between aging and OHT that may help explain the increased prevalence of glaucoma in older humans.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245751","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}

{"title":"A Standardized Protocol for Mouse Longevity Studies in Preclinical Drug Development.","authors":"Alex Zhavoronkov, Qian Wang, Yujie Liu, Wenbin Hou, Yuelei Shen, Dominika Wilczok, Kristen Fortney, Alex Aliper, Man Zhang, Feng Ren, Richard A Miller","doi":"10.14336/AD.2025.0508","DOIUrl":"https://doi.org/10.14336/AD.2025.0508","url":null,"abstract":"<p><p>Although aging is increasingly recognized as a key factor in chronic disease management, preclinical drug development rarely incorporates direct assessments of lifespan. To date, no biotechnology company has conducted a full mouse lifespan study for a therapeutic agent prior to human clinical trials, despite widespread chronic use of many approved drugs. This oversight stems from a lack of standardized protocols for the incorporation of mouse lifespan studies, high costs, limited commercial incentives, and regulatory risks associated with long-term data. Here, we present a comprehensive and scalable protocol for conducting mouse longevity studies in the early stages of drug development. Being aware of monetary constraints in the drug discovery process, we propose a basic design for a longevity study on ~250 (176 males and 72 females) genetically heterogeneous mice (UM-HET3) per group, with survival curves as primary endpoint, and propose enhanced study design options only if budget allows. Our framework provides a standardized foundation for integrating longevity assessments into routine drug development, offering the potential to uncover long-term risks or benefits that traditional toxicology studies may overlook. Broad implementation of such protocols could support the development of safer and more effective therapeutics for chronic diseases, while opening new avenues for discovery of substances that could slow down the rate of aging, known as geroprotectors.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245750","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}

{"title":"Neutrophil Extracellular Traps Promote AIM2-Dependent Microglial Pyroptosis Following Stroke.","authors":"Hanze Chen, Linhui Ni, Jinhua Zhang, Xu Zheng, Yigang Chen, Xing Jin, Beibei Hu, Xinxin Xu, Qiwen Tang, Shuang Li, Yonggang Hao, Shilong Sun, Chengbin He, Shuxia Cao, Xingyue Hu","doi":"10.14336/AD.2024.1733","DOIUrl":"https://doi.org/10.14336/AD.2024.1733","url":null,"abstract":"<p><p>Neutrophils are among the earliest and most abundant immune cells infiltrating the brain following ischemic stroke, aggravating neuroinflammation through the formation of neutrophil extracellular traps (NETs). Pyroptosis, an inflammasome-mediated form of programmed cell death, occurs in post-stroke brain tissue and amplifies inflammation by releasing proinflammatory mediators, propagating the inflammatory cascade. However, the mechanistic link between NETs and pyroptosis remains unclear. This study demonstrated significantly elevated NET levels in arterial blood at the infarct site compared with venous or femoral arterial blood in stroke patients. A positive correlation was observed between the 24-h change in NIHSS score (NIHSS_baseline - NIHSS24h) and the difference in arterial citrullinated histone 3 (CitH3)-DNA (NETs) levels between the infarct site and femoral artery (NET_{sinfarct site} - NET_{sfemoral artery}). In a murine stroke model, NETs were detected in the brain parenchyma. Pharmacological inhibition of NET formation with GSK484, a selective protein-arginine deiminase type 4 antagonist, suppressed NET production, reduced absent in melanoma 2 (AIM2) inflammasome expression, and improved neurological outcomes in mice following stroke. AIM2 knockdown in brain tissue achieved similar neuroprotective effects. In both BV2 cells and stroke-induced mice, NETs triggered AIM2-dependent pyroptosis. These findings suggest that neutrophils in peripheral blood infiltrate the brain parenchyma to generate NETs, activating the AIM2 inflammasome in microglia and exacerbating stroke-induced brain injury through pyroptosis. Targeting NET formation or AIM2 inflammasome activation represents a potential therapeutic strategy for attenuating post-stroke neuroinflammation and secondary neuronal damage.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245754","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}

{"title":"RSV Infection and Neurodegenerative Diseases: A Hypothesis of Energy Metabolism Disruption via the Lung-Brain Axis.","authors":"Zeping Liu, Yan Zhou, Mingming Qi, Fangyuan Ren, Yurong Tan","doi":"10.14336/AD.2025.0534","DOIUrl":"https://doi.org/10.14336/AD.2025.0534","url":null,"abstract":"<p><p>Respiratory Syncytial Virus (RSV), primarily recognized as a respiratory pathogen, has emerged as a potential contributor to neurodegenerative diseases via the \"lung-brain axis.\" Preclinical studies highlight RSV-induced energy metabolism dysfunction as a core pathological mechanism encompassing mitochondrial dysfunction, glucose metabolism reprogramming, and microglial metabolic polarization-critical gaps in clinical validation, molecular specificity, and translational relevance. This review addresses these limitations by advocating for enhanced epidemiological research, detailed molecular pathway characterization, and the integration of human-relevant models. Targeted metabolic interventions have been proposed, supported by recent mechanistic insights, to bridge the gap between hypotheses and therapeutic development.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245756","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}

{"title":"Short-Chain Fatty Acids Improve Hippocampal Atrophy, Ventricular Dilatation and Cognitive Function Decline in Aged Mice.","authors":"Pei-Ju Lee, Yu-Chun Lo, You-Yin Chen, Chaur-Jong Hu, Yen-Kuang Lin, Quoc Thao Trang Pham, Nicholas Keyi Sim, Chee Kin Then, Shing-Chuan Shen","doi":"10.14336/AD.2025.0426","DOIUrl":"https://doi.org/10.14336/AD.2025.0426","url":null,"abstract":"<p><p>Many countries are becoming aged or super-aged societies. This demographic shift causes substantial social, economic, and personal costs directly and indirectly attributable to cognitive decline. Recent studies have shown that dietary fiber can slow down memory decline, with short-chain fatty acids being the primary metabolites produced by gut microbiota from the fermentation of dietary fiber. Despite this, there are limited studies investigating the effect of SCFAs on age-related cognitive function and morphological changes of the brain. In this study, we used B6C3F1 male mice at the age of 3 months and treated them with water, low dose, and high dose SCFAs for 9 months. We assessed their short- and long-term cognitive functions using the Novel Object Recognition test, Morris Water Maze, and Rotarod test. Their brain structure was assessed by 7 Tetra Magnetic Resonance Imaging (7TMRI) and gut microbiota analyzed by 16S rRNA sequencing. Our results show that both short-term and long-term SCFA treatment significantly improve cognitive deficits in the Novel Objective Recognition test and Morris Water Maze tests. Additionally, the 7T MRI results show that SCFAs mitigated hippocampal atrophy compared to the control group. These improvements were accompanied by alteration of gut microbiota composition. We also found that, after treatment, the beneficial gut microbiota Alloprevotella was positively correlated with hippocampal volume. Therefore, we propose that SCFAs may be a promising therapeutic strategy to counteract age-related cognitive decline.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245757","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}

{"title":"The Multimodal Nanomaterials of Phototherapy for Tumor Treatment.","authors":"Yanan Bao, Wenxin Chou, Yusen Hou, Shanlin Yang, Yi Li, Yuxia Zhao, Hongyou Zhao","doi":"10.14336/AD.2025.0448","DOIUrl":"https://doi.org/10.14336/AD.2025.0448","url":null,"abstract":"<p><p>Tumor is a multiple disease in aged people, which seriously threat their physical and mental health. Photodynamic therapy (PDT) as a novel tumor treatment method has been applied in clinic. However, the limited penetration depth of the excitation light and the hypoxic environment of the tumor limit its therapeutic effect. To breakthrough these two bottlenecks, multimodal nanomaterials that combined two or three therapeutic modalities into a single system were designed, which can significantly improve the effectiveness of tumor treatment. This review firstly summarized the nanomaterials that can mediate the combinations between PDT and other strategies, including photothermal therapy (PTT), chemodynamic therapy (CDT), gas therapy (GT), starvation therapy (ST), photoacidity therapy (PAT), and even the synergistic combination of PDT, PTT, and CDT. Furthermore, the advantages and disadvantages of these combination therapies applied in tumor treatment were compared. Eventually, the challenges of these nanomaterials for clinical applications are discussed.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245758","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}

{"title":"Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.","authors":"Gudimetla Susmitha Mohan, Rahul Kumar","doi":"10.14336/AD.2025.0472","DOIUrl":"10.14336/AD.2025.0472","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition defined by the gradual impairment of cognitive functions, synaptic disarray, and extensive neuronal loss. Emerging evidence suggests that metabolic impairment, specifically within tricarboxylic acid (TCA) cycle, is instrumental in the AD pathophysiology. TCA cycle represents an indispensable pathway in metabolism that is responsible for energy production, and the maintenance of cellular homeostasis, particularly in neurons. Several in vitro, clinical, and in vivo studies reported that several TCA cycle enzymes disrupt during AD. Disruption in TCA cycle enzymes exhibits more pronounced impact on the brain owing to its high metabolic activity and continuous demand for energy, where any reduction in ATP production can severely impair neuronal function, synaptic plasticity, and overall cognitive processes. The current review explores the mechanisms underlying AD related impairment in TCA cycle, focussing on the molecular alterations of TCA enzymes. We also discussed potential activators and inhibitors of TCA cycle enzymes as a potential therapeutic intervention to restore AD related metabolic balance.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":"2553-2574"},"PeriodicalIF":6.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245753","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}

{"title":"Soluble Epoxide Hydrolase Inhibition Improves Alzheimer's Disease Hallmarks: Correlation with Peripheral Inflammation and Gut Microbiota Modulation.","authors":"Júlia Jarne-Ferrer, Christian Griñán-Ferré, Beatrice Jora, Sandra Codony, Lluïsa Miró, Cristina Rosell-Cardona, David Miñana-Galbis, Anna Pérez-Bosque, Santiago Vazquez, Mercè Pallàs","doi":"10.14336/AD.2025.0201","DOIUrl":"https://doi.org/10.14336/AD.2025.0201","url":null,"abstract":"<p><p>Targeting brain inflammation has been proposed as a promising therapeutic strategy to cope with neurodegenerative diseases. Interestingly, accumulating data suggest that the gut microbiota partially exerts its neurodegenerative effects by exacerbating neuroinflammation through increased pathogenic or unhealthy genera that releases different types of cytokines in the periphery. Recently, soluble epoxide hydrolase enzyme (sEH) emerged as a new pharmacological approach for treating Alzheimer's Disease. Treatment with a sEH inhibitor (UB-BJ-02) modified the gut microbiota in the 5xFAD mouse model, increasing health-promoting genera such as Lactobacillus and Limosilactobacillus. By contrast, pro-inflammatory genera (e.g., Bacteroides) were decreased. UB-BJ-02 treatment enhanced the production of anti-inflammatory peripheral mediators in the colon and spleen, such as Il-10. 5xFAD mice treated with UB-BJ-02 showed improved short- and long-term memory and spatial memory compared to 5xFAD control. Furthermore, we found a reduction in neuroinflammatory markers evaluated by immunohistochemical assays, such as GFAP and IBA-1, and gene expression, such as Il-1β, Tnf-a, Il-6, and Trem2, in the brain of 5xFAD-treated mice and a significant decrease in the number of Aβ plaques. T Treatment decreased DRP1 protein levels while increasing OPA1 levels, resulting in improved mitochondrial function corroborated by the elevation of Pgc1-α. Interestingly, a correlation between UB-BJ-02 brain effects and microbiota changes were demonstrated. To validate this correlation, we fed CL4176 AD transgenic strain, with Limosilactobacillus reuteri and Bacteroides rodentium. Consequently, we observed that changes in feeding modified the number of Aβ plaques and neuroinflammatory markers in C. elegans. Therefore, the present study suggested that sEH inhibition with UB-BJ-02 promoted neuroprotective effects, modulating gut microbiota and modifying peripheral and brain pro-inflammatory markers.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148756","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}

{"title":"Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.","authors":"Ziran Zhang, Xiaolin He, Yuxin Sun, Jitong Li, Jia Sun","doi":"10.14336/AD.2025.0233","DOIUrl":"https://doi.org/10.14336/AD.2025.0233","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic high blood sugar levels and insulin resistance (IR). Modern medicine has shown that diabetes plays a role in speeding up the aging process of the body independently of age, making it an age-related aging disease. The oxidative stress caused by chronic high blood sugar and IR can lead to dysfunctional mitochondria, which in turn promotes changes in epigenetic regulation, shortening of telomeres, and cellular senescence. There is currently a lot of interest in understanding how T2DM contributes to senescence. This review synthesizes epidemiological and clinical research findings on aging across various organs, focusing on insulin resistance and oxidative stress as primary mechanisms. It introduces four diabetes-specific aging axes: glucose toxicity, toxicity of advanced glycation end-products (AGEs), immunoinflammatory aging, and protein amyloidosis, which are integrated into the \"metabolism-inflammation-aging\" network. Additionally, we provide new insights into interventions targeting aging in diabetes.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148759","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}

{"title":"A Comprehensive Review of the Correlations of Measurement Parameters among Modern Technologies for Sarcopenia Assessment.","authors":"Dawei Zhang, Sai Kit Lam, Yongping Zheng","doi":"10.14336/AD.2025.0145","DOIUrl":"https://doi.org/10.14336/AD.2025.0145","url":null,"abstract":"<p><p>Sarcopenia is characterized by a degeneration of muscle mass and strength, which impairs mobility and causes fragility in older adults. Modern assessment technologies include magnetic resonance imaging (MRI), computed tomography (CT), bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and ultrasound (US). Despite the tremendous efforts made in the past to investigate the correlations among measurement parameters of these technologies, inconsistencies in the reported correlations persist, and there is no existing review article considering all these technologies for sarcopenia assessment, resulting in a lack of a common understanding about the correlations of these techniques. Herein, we conduct a comprehensive review to scrutinize the reported correlations between each pair of these five technologies from 51 publications in the literature. We classified these five technologies into two categories: image-based methods (IBMs), including CT, MRI, and US, and non-image-based methods (NIBMs), including DXA and BIA, resulting in ten pairs of correlations analyzed. The averaged correlations for NIBM-NIBM (BIA-DXA: 0.909) and IBM-IBM (MRI-CT: 0.978; MRI-US: 0.861; CT-US: 0.875; overall: 0.905) were high, while those for NIBM-IBM exhibited lower correlations with wider variations (DXA-CT: 0.834; BIA-CT: 0.824; BIA-MRI: 0.715; DXA-MRI: 0.834; DXA-US: 0.497; and BIA-US: 0.463; overall: 0.695). Generally, the correlations within the same category were greater than those between different categories. The dissimilar measurement locations and components could apparently cause lower correlations (e.g., BIA-US and DXA-US); the lower averaged correlations do not necessarily represent their low clinical value for sarcopenia assessments. By contrast, integrating NIBM and IBM may leverage the strengths of each technology, complementing their metrics, and bring a more holistic connection to sarcopenia. We hope to facilitate an enhanced understanding of the reported correlations from the literature, offering the community insightful recommendations for selecting technologies toward further research.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245749","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}