Aging and Disease最新文献_第2页

LLMs and AI Life Models for Traditional Chinese Medicine-derived Geroprotector Formulation. 中医药衍生Geroprotector配方的llm和AI生命模型。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-17 DOI: 10.14336/AD.2024.1697

Fedor Galkin, Feng Ren, Alex Zhavoronkov

{"title":"LLMs and AI Life Models for Traditional Chinese Medicine-derived Geroprotector Formulation.","authors":"Fedor Galkin, Feng Ren, Alex Zhavoronkov","doi":"10.14336/AD.2024.1697","DOIUrl":"https://doi.org/10.14336/AD.2024.1697","url":null,"abstract":"Traditional Chinese Medicine (TCM) represents a vast repository of therapeutic knowledge, but its integration with modern drug discovery remains challenging due to fundamental differences in theoretical frameworks. We developed an AI agent-driven framework combining Precious3GPT (P3GPT), a multi-omics transformer model, with the BATMAN-TCM2 database of TCM compound-target interactions to bridge this gap. As a proof-of-concept, we used P3GPT-generated cross-species and cross-tissue signatures to screen TCM compounds, herbs, and formulas to identify novel natural geroprotectors. The cross-species analysis identified 13 conserved aging-associated genes, leading to the identification of 34 TCM compounds with significant target overlap and enabling identification of HUA SHAN WU ZI DAN and other TCM formulations as a promising historical formula. Our work demonstrates the feasibility of using AI to systematically bridge TCM and modern pharmacology, enabling rational design of multi-component formulations targeting age-related processes across multiple tissues and species. This approach provides a framework for modernizing traditional medicine while maintaining its holistic therapeutic principles. To help other teams integrate AI experimentation in their research process, we publicly release all materials and codebase used in this work, including the multi-agent system, cross-species and cross-tissue signatures of aging, as well as TCM databases formatted for AI interactions.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961778","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

Unraveling Homocysteine's Role in Dementia: No Specific Association with Alzheimer's Disease, but a Connection to White Matter Hyperintensities. 揭示同型半胱氨酸在痴呆中的作用：与阿尔茨海默病没有特定的联系，但与白质高强度有关。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-15 DOI: 10.14336/AD.225.0020

Théodore Decaix, Matthieu Lilamand, Karl Götze, François Mouton-Liger, Emmanuel Cognat, Jacques Hugon, Elodie Bouaziz-Amar, Louise Sindzingre, Julien Dumurgier, Claire Paquet

{"title":"Unraveling Homocysteine's Role in Dementia: No Specific Association with Alzheimer's Disease, but a Connection to White Matter Hyperintensities.","authors":"Théodore Decaix, Matthieu Lilamand, Karl Götze, François Mouton-Liger, Emmanuel Cognat, Jacques Hugon, Elodie Bouaziz-Amar, Louise Sindzingre, Julien Dumurgier, Claire Paquet","doi":"10.14336/AD.225.0020","DOIUrl":"https://doi.org/10.14336/AD.225.0020","url":null,"abstract":"Hyperhomocysteinemia (HHcy) is an established risk factor for cognitive impairment. The specific role of HHcy in the pathophysiology of Alzheimer's disease (AD) is debated, as most of the suspected mechanisms overlap with those of vascular dementia (VD). The aim of this study was to explore the association between plasma homocysteine (Hcy) levels and cerebrospinal fluid (CSF) biomarkers of AD, as well as brain magnetic resonance imaging (MRI) features. Cross-sectional observational analysis from a single-center tertiary memory clinic. We first assessed the association between Hcy in tertiles and the CSF AD biomarkers (according to the Amyloid (A) Tau (T) Neurodegeneration (N) classification) with further adjustments for age and sex. Then, we analyzed the relationship between HHcy and hippocampal atrophy (Scheltens scale) and white matter lesions (WML) (Fazekas scale) on brain MRI. We included 507 patients [mean age 68.9 (standard deviation=8.9)] with mean plasma Hcy at 13.3 (4.7) μmol/L in this study. There was no significant association between Hcy tertiles and CSF AD biomarkers. Plasma Hcy levels showed no correlation with any CSF AD biomarkers. The severity of WML increased with higher Hcy tertiles (p&;lt0.0001). Patients with a CSF AD (A+T+) profile exhibited elevated mean Hcy levels when they presented moderate to severe WML (p&;lt0.0001). Our findings challenge the link between Hcy and AD pathophysiology while highlighting a significant connection between Hcy and microvascular cognitive impairment. Further longitudinal studies are needed to validate these conclusions.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961957","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

NK Cell Senescence in Cancer: From Molecular Mechanisms to Therapeutic Opportunities. 癌症中NK细胞衰老：从分子机制到治疗机会。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-12 DOI: 10.14336/AD.2025.0053

Zilin Qiu, Zhengrui Li, Cangang Zhang, Qun Zhao, Zaoqu Liu, Quan Cheng, Jian Zhang, Anqi Lin, Peng Luo

{"title":"NK Cell Senescence in Cancer: From Molecular Mechanisms to Therapeutic Opportunities.","authors":"Zilin Qiu, Zhengrui Li, Cangang Zhang, Qun Zhao, Zaoqu Liu, Quan Cheng, Jian Zhang, Anqi Lin, Peng Luo","doi":"10.14336/AD.2025.0053","DOIUrl":"https://doi.org/10.14336/AD.2025.0053","url":null,"abstract":"P Natural killer (NK) cells function as crucial effectors in the innate immune response against tumors. Nevertheless, NK cell senescence, characterized by phenotypic and functional changes, substantially compromises their antitumor immune response. This review provides a comprehensive summary of the molecular mechanisms governing NK cell senescence and its implications for cancer immunotherapy. We propose a refined definition of NK cell senescence based on distinct biomarkers, including elevated CD57 expression, reduced cytotoxicity, and altered cytokine secretion. Moreover, we investigate the complex interactions between the tumor microenvironment (TME) and NK cell senescence, highlighting the influence of chronic inflammation, immunosuppressive cytokines, and persistent tumor antigenic stimulation. Additionally, this review underscores the potential utility of senescent NK cells as biomarkers for assessing antitumor efficacy and examines the adverse effects of NK cell senescence on cancer immunotherapy. Lastly, we summarize current approaches to mitigate NK cell senescence, such as gene editing techniques and cytokine modulation, which may enhance the efficacy of NK cell-based immunotherapies. By establishing a comprehensive framework for understanding NK cell senescence within the TME, this review aims to guide future research and the development of innovative therapeutic strategies targeting senescent NK cells to improve cancer immunotherapy outcomes.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958951","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

Plasma Interferon-gamma is Associated with Poor Treatment Response in Neovascular Age-Related Macular Degeneration. 血浆干扰素γ与新生血管性年龄相关性黄斑变性治疗不良反应相关

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-09 DOI: 10.14336/AD.2024.1585

Alexander Kai Thomsen, Maria Abildgaard Steffensen, Jenni Martinez Villarruel Hinnerskov, Amalie Thomsen Nielsen, Henrik Vorum, Bent Honoré, Mogens Holst Nissen, Torben Lykke Sørensen

{"title":"Plasma Interferon-gamma is Associated with Poor Treatment Response in Neovascular Age-Related Macular Degeneration.","authors":"Alexander Kai Thomsen, Maria Abildgaard Steffensen, Jenni Martinez Villarruel Hinnerskov, Amalie Thomsen Nielsen, Henrik Vorum, Bent Honoré, Mogens Holst Nissen, Torben Lykke Sørensen","doi":"10.14336/AD.2024.1585","DOIUrl":"https://doi.org/10.14336/AD.2024.1585","url":null,"abstract":"Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly. Aging is the most important risk factor for AMD, and the aging immune system seems to be involved in pathogenesis. This study investigates the systemic aging immune profile in relation to AMD stage and treatment response. Treatment-naïve patients with neovascular AMD (nAMD), intermediate AMD and healthy controls were included in this prospective study. Participants were examined for systemic aging immune profiles and compared to AMD stage, as well as initial and one-year treatment response in nAMD patients. Flowcytometry was performed to determine T cell differentiation (naïve, central memory and effector memory) and expression of costimulatory markers (CD27, CD28, CD56). Cytokine assays were performed to measure the concentrations of plasma cytokines IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-27, TNF-α. Polymorphisms of CFH and ARMS2 genes were compared in nAMD patients. Patients with nAMD had significantly higher proportions of central and effector memory CD8+ T cells compared to controls (both P &;lt 0.036). nAMD patients had significantly elevated concentrations of IFN-γ, IL-1β, IL-2, and IL-10 (all P &;lt 0.05). nAMD patients with poor initial treatment response had a significantly higher concentration of plasma IFN-γ compared to good responders (P =0.026). Patients with nAMD had a more advanced systemic aging immune profile with higher levels of T cell differentiation and plasma cytokines compared to controls. Poor initial response had elevated levels of plasma IFN-γ compared to good responders in nAMD.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958171","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

Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging? 唐氏综合征线粒体失衡：脑加速衰老的驱动因素？

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-08 DOI: 10.14336/AD.2025.0189

Xinxin Zuo

引用次数: 0

Dual Challenges in the Context of Healthy Aging: A Comprehensive Exploration of the Association Between Malnutrition and Cognitive Decline in Disabled Elderly. 健康老龄化背景下的双重挑战：残疾老年人营养不良与认知能力下降关系的综合探讨。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-08 DOI: 10.14336/AD.2025.0337

Runyuan Yu, Lixia Wang, Yifan Liu, Yimeng Hu, Zuncheng Zheng, Xiaoyu Wang, Yuexia Chen, Yulian Liu

{"title":"Dual Challenges in the Context of Healthy Aging: A Comprehensive Exploration of the Association Between Malnutrition and Cognitive Decline in Disabled Elderly.","authors":"Runyuan Yu, Lixia Wang, Yifan Liu, Yimeng Hu, Zuncheng Zheng, Xiaoyu Wang, Yuexia Chen, Yulian Liu","doi":"10.14336/AD.2025.0337","DOIUrl":"https://doi.org/10.14336/AD.2025.0337","url":null,"abstract":"Disabled older adults represent a population requiring special attention in the context of global aging, with malnutrition and cognitive decline being prevalent and interrelated health concerns. This review systematically examines the association between malnutrition and mental deterioration in this population, with an in-depth exploration of the potential biological mechanisms underlying this relationship. Current evidence suggests that malnutrition accelerates cognitive decline through multiple pathways, including neurotransmitter synthesis impairment, insufficient cerebral energy supply, chronic inflammation and oxidative stress, blood-brain barrier dysfunction, and reduced neuroplasticity. Additionally, dysregulation of the gut-brain axis, an emerging mechanism, may influence brain health via alterations in the gut microbiota. This review aims to provide a theoretical foundation for understanding the intricate relationship between malnutrition and cognitive impairment while offering insights into optimizing health management and nutritional strategies for disabled older adults.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964354","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

SLC7A11 in Fibrosis: Molecular Mechanisms and Future Prospects. SLC7A11在纤维化中的分子机制及未来展望

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-06 DOI: 10.14336/AD.2025.0106

Juntong Chen, Yanjie He, Ru Chen, Zhiyong Yang, Xiaomeng Luo, Fan Yang

引用次数: 0

Green Tea Mitigates the Hallmarks of Aging and Age-Related Multisystem Deterioration. 绿茶减轻衰老和与年龄相关的多系统退化的标志。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-05 DOI: 10.14336/AD.2025.0398

Yusuf Yilmaz

{"title":"Green Tea Mitigates the Hallmarks of Aging and Age-Related Multisystem Deterioration.","authors":"Yusuf Yilmaz","doi":"10.14336/AD.2025.0398","DOIUrl":"https://doi.org/10.14336/AD.2025.0398","url":null,"abstract":"Aging is characterized by progressive multisystem deterioration driven by molecular and cellular mechanisms encapsulated in the twelve hallmarks of aging. Green tea (GT), derived from Camellia sinensis, has garnered significant scientific interest due to its rich polyphenolic composition, particularly epigallocatechin-3-gallate, and its pleiotropic health benefits. In this narrative review, we explored the multifaceted mechanisms through which GT may mitigate the aging hallmarks. Evidence from in vitro, animal, and human studies has shown that GT polyphenols can enhance DNA repair pathways, preserve telomere length, modulate epigenetic aging markers, improve proteostasis and autophagic flux, regulate nutrient-sensing networks, and rejuvenate mitochondrial function. Additionally, GT exhibits anti-inflammatory properties and may restore a physiological gut microbiota composition. Beyond molecular and cellular effects, GT consumption in humans has been associated with improved cognitive function, cardiovascular health, muscle preservation, and metabolic regulation in aging populations. Collectively, these findings highlight GT's potential as a naturally occurring geroscience intervention capable of addressing the interconnected network of aging processes more comprehensively than single-target pharmaceuticals. Future research should focus on optimizing dosing regimens, exploring synergies with other anti-aging strategies, and investigating personalized responses to GT interventions.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958521","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

Predictive Value of Sarcopenia and Cognitive Decline in Hospitalized Older Adults. 住院老年人肌肉减少症和认知能力下降的预测价值。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-05 DOI: 10.14336/AD.2025.0418

Xiaoyan Hu, Peng Sun

引用次数: 0

Exploring the Role of RhoA/ROCK Signaling in Pain: A Narrative Review. 探索RhoA/ROCK信号在疼痛中的作用：一个叙事回顾。

IF 7 2区医学

Aging and Disease Pub Date : 2025-04-04 DOI: 10.14336/AD.2024.1539

Nan Chen, Ye Tu, Dai-Qiang Liu, Yi Zhang, Yu-Ke Tian, Ya-Qun Zhou, Shao-Bing Yang

引用次数: 0