Ageing Research Reviews最新文献_第10页

Proteomics of In Vivo models of ischemic stroke: A systematic review with a systems biological perspective 缺血性脑卒中体内模型的蛋白质组学：系统生物学视角的系统综述。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-07 DOI: 10.1016/j.arr.2025.102937

Anaekshi Gogoi , Manju Babu , Abhina Gangadhar , Riyama Shirin , Deepthi Ann Thomas , Jasmitha Jayaram , Pratik Thakkar , Arnab Datta

Background and Purpose

To discover therapeutic targets and biomarkers for ischemic stroke, a systems-level understanding of the altered brain proteome is necessary from various types of in vivo models. In the last two decades, despite accumulating numerous large-scale proteomics datasets on in vivo models of ischemic stroke, systematic classification and summarization of these data have not been attempted yet.

Methods

Following PRISMA, ARRIVE, and CAMARADES guidelines, we conducted a systematic review of proteomics studies done on various in vivo models of ischemic stroke (ivProt studies).

Results

Of 680 studies, 120 ivProt studies were shortlisted. They were classified based on TOAST stroke subtypes, model category, study duration, and sampled brain location. We collated 288 proteins deregulated in the brain tissue of MCAO-affected animals, 44 of which were reported in minimum two ivProt studies. A comparison of deregulated proteome between ivProt and clinical proteomics studies revealed consistent deregulation for 85 % of the commonly quantified proteins. The Gene Ontology analysis of the consensus stroke-perturbed proteome (n = 90) showed enrichment of annotation terms related to blood coagulation, HIF-signaling and secretory pathway. About 88 % of these proteins were found listed in an exosome database (ExoCarta), while 42 % overlapped with the therapeutic target database. Notably, this list contained eight successful drug targets (ANXA1, C3, DPYSL2, IDH1, IDH3A, PRKCE, PRKCG, and SERPINA1).

Conclusion

A web resource (ivProt_Repository) was created that may stimulate clinical validation of shortlisted proteins for biomarker discovery or proof-of-concept studies for therapeutic target discovery and help to establish novel pipelines for big data integration.

背景和目的：为了发现缺血性卒中的治疗靶点和生物标志物，有必要从各种类型的体内模型中了解改变的脑蛋白质组。在过去的二十年中，尽管积累了大量关于缺血性卒中体内模型的大规模蛋白质组学数据集，但尚未尝试对这些数据进行系统的分类和总结。方法：遵循PRISMA、ARRIVE和CAMARADES指南，我们对各种缺血性卒中体内模型的蛋白质组学研究（ivProt研究）进行了系统回顾。结果：在680项研究中，有120项ivProt研究入围。他们根据TOAST中风亚型、模型类别、研究持续时间和采样的大脑位置进行分类。我们在受mcao影响的动物脑组织中整理了288个失调控蛋白，其中44个蛋白在至少两项ivProt研究中被报道。在ivProt和临床蛋白质组学研究之间的解除调控蛋白质组的比较显示，85%的常用定量蛋白质一致解除调控。对共识卒中干扰蛋白组（n= 90）的基因本体分析显示，与凝血、hif信号和分泌途径相关的注释术语丰富。这些蛋白中约88%被发现列在外泌体数据库（ExoCarta）中，而42%与治疗靶点数据库重叠。值得注意的是，该列表包含8个成功的药物靶点（ANXA1、C3、DPYSL2、IDH1、IDH3A、PRKCE、PRKCG和SERPINA1）。结论：创建了一个网络资源（ivProt_Repository），可以刺激候选蛋白质的临床验证，用于生物标志物的发现或治疗靶点发现的概念验证研究，并有助于建立新的大数据集成管道。

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引用次数: 0

Irisin-mediated hepatic autophagy remodels nutritional metabolism to prevent cognitive dysfunction 鸢尾素介导的肝自噬重塑营养代谢预防认知功能障碍。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-07 DOI: 10.1016/j.arr.2025.102936

Xinjie Zhang, Yizhuo Yang, Hanan Song, Xuan Hu, Xiaobing Wang, Yanli Yu

Cognitive impairment has emerged as a serious global health challenge and is closely associated with metabolic disorders. Autophagy dysfunction leading to metabolic disorders has become a key factor in neurodegenerative diseases. The liver, as the central organ of systemic metabolism, regulates metabolic homeostasis through hepatic autophagy, thereby affecting the clearance of toxic proteins in the brain and energy supply. Hepatic autophagy dysfunction can increase free fatty acids, which attack the blood-brain barrier and lead to neurodegenerative diseases. Irisin enters the liver via the bloodstream, activates AMPK to promote hepatic autophagy, reduces the production of lipotoxic substances, alleviates neuroinflammation, and ensures effective synaptic signaling. Previous studies have demonstrated that irisin can improve neurodegenerative diseases, but no connection has yet been established between irisin, hepatic autophagy, and cognition. Therefore, this review discusses the positive role of irisin in preventing cognitive impairment through hepatic autophagy. Future studies should employ multi-omics approaches to deeply analyze the metabolic network regulated by irisin and explore its potential in the treatment of neurological diseases. Irisin is expected to serve as a key bridge connecting exercise, metabolic health, and neuroprotection, thus paving the way for the prevention and treatment of cognitive decline and neurodegenerative diseases.

认知障碍已成为一项严重的全球健康挑战，并与代谢紊乱密切相关。自噬功能障碍导致代谢紊乱已成为神经退行性疾病的关键因素。肝脏作为全身代谢的中枢器官，通过肝脏自噬调节代谢稳态，从而影响脑内有毒蛋白的清除和能量供应。肝自噬功能障碍会增加游离脂肪酸，从而攻击血脑屏障，导致神经退行性疾病。鸢尾素通过血流进入肝脏，激活AMPK促进肝脏自噬，减少脂毒性物质的产生，减轻神经炎症，确保有效的突触信号传导。先前的研究表明鸢尾素可以改善神经退行性疾病，但尚未建立鸢尾素与肝自噬和认知之间的联系。因此，本文就鸢尾素在通过肝自噬预防认知功能障碍中的积极作用进行综述。未来的研究应采用多组学方法，深入分析鸢尾素调控的代谢网络，探索鸢尾素在神经系统疾病治疗中的潜力。鸢尾素有望成为连接运动、代谢健康和神经保护的关键桥梁，从而为预防和治疗认知能力下降和神经退行性疾病铺平道路。

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引用次数: 0

In-hospital exercise interventions improve inpatients’ frailty and demonstrate promising implementation outcomes: A systematic review and meta-analysis 住院运动干预改善住院病人虚弱和展示有希望的实施结果：系统回顾和荟萃分析。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-06 DOI: 10.1016/j.arr.2025.102934

Madeline E. Shivgulam , Haoxuan Liu , Zainab Zafar , Muhammad Cheema , Shirko Ahmadi , Olga Theou , Myles W. O’Brien

Background

Frail, hospitalized patients are at a greater risk of further health issues. Frailty levels can worsen during hospitalization, with exercise being one of the best strategies to manage frailty. However, there is a lack of synthesized evidence to indicate whether exercise interventions are effective at managing frailty in this unique setting.

Objective

This systematic review and meta-analysis determined if exercise interventions either preserve or improve frailty levels among inpatients.

Methods

Sources were searched in May 2024 (updated August 2025) and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier. Studies were included if they conducted an exercise intervention in middle-to-older adult (≥45-years) inpatients and assessed frailty as an outcome using any validated frailty assessment tool. The between-group effect size of change in frailty (Intervention vs. Control) was calculated as the standardized mean difference (SMD) using a random effects model.

Results

Five studies including n = 810 intervention (age: 82.9 [range: 79–87.6] years; 45 ± 1 % reported females) and 900 control (age: 82.0 [range: 76.0–87.1] years; 44 ± 1 % reported females) participants were included. Improvements in patients’ frailty were observed in n = 3/5 studies. The meta-analysis exhibited a favorable effect on frailty between the intervention and control groups (SMD: 0.716, 95 %CI: 0.119–1.312) with significant heterogeneity between studies (I²=92 %, p < 0.001). No differences were observed between interventions using distinct exercise types or frailty assessment tools (both, p > 0.196).

Conclusion

Despite limited available evidence, results indicate exercise training interventions may be effective in improving frailty. This supports the inclusion of exercise interventions beyond usual hospital care to improve frailty.

背景：体弱的住院患者出现进一步健康问题的风险更大。在住院期间，虚弱程度可能会恶化，锻炼是控制虚弱的最佳策略之一。然而，缺乏综合证据表明，在这种独特的环境下，运动干预是否能有效地控制虚弱。目的：本系统综述和荟萃分析确定运动干预是否能保持或改善住院患者的虚弱水平。方法：检索于2024年5月（更新于2025年8月）的文献，包括Scopus、EMBASE、MEDLINE、CINAHL和Academic Search Premier。纳入对中老年住院患者（≥45岁）进行运动干预的研究，并使用任何经过验证的衰弱评估工具评估衰弱作为结果。采用随机效应模型计算虚弱变化（干预组与对照组）的组间效应量为标准化平均差（SMD）。结果：共纳入5项研究，其中干预组810例（年龄：82.3±3.5[范围：79-87.6]岁，女性45±1%），对照组900例（年龄：81.6±4.1[范围：76.0-87.1]岁，女性44±1%）。在n=3/5的研究中观察到患者虚弱的改善。meta分析显示，干预组和对照组对虚弱有良好的影响（SMD: 0.716, 95%CI: 0.119 ~ 1.312），研究间存在显著的异质性（I2=92%, p0.196）。结论：尽管现有证据有限，但结果表明运动训练干预可能有效改善虚弱。这支持在常规医院护理之外纳入运动干预以改善虚弱。

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引用次数: 0

Ferroptosis and pyroptosis: Mediating mechanisms of the cGAS/STING pathway and therapeutic strategies in heart failure 铁下垂和焦下垂：cGAS/STING通路的介导机制和心力衰竭的治疗策略。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-05 DOI: 10.1016/j.arr.2025.102932

Zeyu Zhang , Zhihua Yang , Shuai Wang , Xianliang Wang , Jingyuan Mao

Focusing on cardiomyocyte survival in the prevention and treatment of heart failure, ferroptosis and pyroptosis—two vital modes of cell death—have attracted intense interest. The immunomodulatory cGAS/STING axis, a currently prominent pathway, has also been found to mediate both ferroptosis and pyroptosis; however, the underlying mechanisms remain unclear. This review first traces the historical development of ferroptosis and pyroptosis, dissecting their distinctions, interconnections, and molecular biology. It then spotlights the cGAS/STING axis, elucidating the structural hallmarks of its core proteins, the cascade of signal activation and propagation, its self-amplifying feedback loop, and the precise routes through which it orchestrates ferroptosis and pyroptosis, while also revealing how these two death modalities in turn reinforce the pathway. Furthermore, we investigate the combined effects of ferroptosis and pyroptosis on cardiac structure and function, and rigorously evaluate emerging therapeutic strategies targeting the cGAS/STING axis, encompassing chemical drugs, bioactive natural compounds, small-molecule antagonists, genetic interventions, and exercise training. By integrating the axis’s dual role in counteracting pyroptosis and ferroptosis, the review highlights the cGAS/STING pathway as a central target in heart failure management, offering insights to advance both theoretical frameworks and practical therapeutic avenues.

关注心肌细胞存活在预防和治疗心力衰竭中的作用，铁亡和热亡这两种重要的细胞死亡模式引起了人们的强烈兴趣。免疫调节的cGAS/STING轴，一个目前突出的途径，也被发现介导铁下垂和焦亡；然而，潜在的机制仍不清楚。本文首先回顾了铁下垂和焦下垂的历史发展，剖析了它们的区别、相互联系和分子生物学。然后聚焦cGAS/STING轴，阐明其核心蛋白的结构特征，信号激活和传播的级联，其自我放大的反馈回路，以及它协调铁亡和焦亡的精确途径，同时也揭示了这两种死亡模式如何反过来加强该途径。此外，我们研究了铁亡和焦亡对心脏结构和功能的综合影响，并严格评估了针对cGAS/STING轴的新兴治疗策略，包括化学药物、生物活性天然化合物、小分子拮抗剂、遗传干预和运动训练。通过整合轴在对抗焦亡和铁亡中的双重作用，该综述强调了cGAS/STING途径作为心力衰竭管理的中心靶点，为推进理论框架和实际治疗途径提供了见解。

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引用次数: 0

The potential of marine-derived compounds in geroscience 海洋衍生化合物在古科学中的潜力。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-05 DOI: 10.1016/j.arr.2025.102935

Maria Elisa Giuliani , Chiara Giordani , Gianmarco Bertoni , Emanuele Francini , Giorgia Bigossi , Giovanni Lai , Serena Marcozzi , Sunday Segun Alimi , Davide Perini , Andrea Piccinini , Sara Ristori , Elisa Bientinesi , Francesca Barone , Maurizio Cardelli , Cesare Indiveri , Mariafrancesca Scalise , Daniela Monti , Marco Malavolta

Aging is a natural, multifactorial biological process characterized by progressive cellular and tissue damage in response to various stressors, leading to functional decline that often affects multiple organs, contributing to the development of age-related diseases. Although life expectancy has increased significantly, age-related conditions have become the leading causes of impairment and disability in the elderly, becoming a major global health concern. This highlights the need for innovative, multitarget strategies to modulate the aging process and extend healthspan. In recent years, researchers have explored natural solutions to counteract the hallmarks of aging. Among these, marine-derived molecules represent an up-and-coming niche of bioactive compounds, distinguished by their unique structural diversity and multifunctional properties. Marine products are increasingly studied for their antioxidant, anti-inflammatory and cytoprotective properties, targeting key pathways involved in aging, such as cellular senescence, genomic instability, impaired autophagy, and chronic inflammation. In this review, we aim to (i) explore the field of marine-derived bioactive molecules which demonstrated effects on lifespan extension, (ii) summarize studies showing their capacity to target one or more hallmarks of aging, (iii) highlight those that exhibit therapeutic potential in age-related diseases – including neurodegenerative, cardiovascular, metabolic, cancer, musculoskeletal, and chronic pulmonary disorders. Their multitarget activity makes them attractive candidates for the prevention or treatment of age-related diseases, and several have shown promising results in preclinical studies. However, only a limited number of these compounds have progressed to late-stage clinical trials, highlighting the need for further translational research, which may pave the way for novel anti-aging therapeutic strategies.

衰老是一种自然的、多因素的生物过程，其特征是细胞和组织在各种应激源的作用下受到进行性损伤，导致功能下降，往往影响多个器官，从而导致与年龄有关的疾病的发生。虽然预期寿命已大大延长，但与年龄有关的疾病已成为老年人受损和残疾的主要原因，成为一个主要的全球健康问题。这突出表明需要创新的多目标战略来调节老龄化进程和延长健康寿命。近年来，研究人员探索了对抗衰老特征的自然解决方案。其中，海洋衍生分子以其独特的结构多样性和多功能特性，代表了生物活性化合物的一个新兴利基。海洋产品因其抗氧化、抗炎和细胞保护特性而受到越来越多的研究，这些特性针对与衰老有关的关键途径，如细胞衰老、基因组不稳定、自噬受损和慢性炎症。在这篇综述中，我们的目标是(i)探索海洋来源的生物活性分子领域，这些生物活性分子已经证明对延长寿命有影响，（ii）总结研究表明它们能够针对一种或多种衰老特征，（iii）强调那些在与年龄相关的疾病中显示出治疗潜力的生物活性分子，包括神经退行性疾病、心血管疾病、代谢疾病、癌症、肌肉骨骼疾病和慢性肺部疾病。它们的多靶点活性使它们成为预防或治疗年龄相关疾病的有吸引力的候选者，其中一些在临床前研究中显示出有希望的结果。然而，只有有限数量的这些化合物进入了后期临床试验，这突出了进一步的转化研究的必要性，这可能为新的抗衰老治疗策略铺平道路。

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引用次数: 0

Exploring the causal relationship between telomere regulation, aging and neurological disorders 探讨端粒调节、衰老和神经系统疾病之间的因果关系。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-05 DOI: 10.1016/j.arr.2025.102930

Gaurav Gupta , Haider Ali , Sachin Kumar Singh , Kamal Dua , Saurabh Kumar Jha

Telomere biology is important for aging and is the cause of the pathogenesis of many neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and brain tumors. Telomere shortening is considered to play a role in neurodegeneration, immune senescence, and cerebrovascular dysfunction. Shorter leukocyte telomere length (LTL) is associated with increased risk and severity of stroke, poorer cognitive outcomes in AD, and increased neuroinflammation in MS, highlighting a possible biomarker for disease progression. Glioblastoma and medulloblastoma are characterized as adult and childhoodd neoplasms,respectively; however they aree similarinn terms of telomere regulatio,nwhicht allows malignant growth. However, disease pathophysiology has been associated with telomere dynamics, oxidative stress, and neuroinflammation, but the causal association between telomere attrition and neurological disorders is still unclear. In studies of Mendelian randomization, neurodegenerative diseases have been associated with telomere length regulation in addition to telomere attrition. Approaches to target telomeres include telomerase activators for neuroprotection, telomerase inhibitors, and ALT-directed therapies for brain tumors. These telomere-derived biomarkers should be further refined, and their mechanistic links to the acceleration of neurodegeneration should be determined. Telomere-modifying therapies should be balanced to optimize benefits with minimal oncogenic risks. This review explores the causal relationship between telomere biology, aging, and neurological disorders, indicating novel therapeutic strategies and future directions in telomere research.

端粒生物学对衰老很重要，也是许多神经系统疾病的发病机制，包括阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化症（MS）、中风和脑肿瘤。端粒缩短被认为在神经退行性变、免疫衰老和脑血管功能障碍中起作用。较短的白细胞端粒长度（LTL）与卒中风险和严重程度增加、AD患者认知结果较差以及MS患者神经炎症增加相关，这突出了疾病进展的可能生物标志物。胶质母细胞瘤和髓母细胞瘤分别以成人和儿童肿瘤为特征；然而，它们在端粒调控方面是相似的，这使得恶性生长成为可能。然而，疾病病理生理与端粒动力学、氧化应激和神经炎症有关，但端粒损耗与神经系统疾病之间的因果关系尚不清楚。在孟德尔随机化的研究中，神经退行性疾病除了与端粒磨损外，还与端粒长度调节有关。靶向端粒的方法包括用于神经保护的端粒酶激活剂、端粒酶抑制剂和用于脑肿瘤的alt定向治疗。这些端粒衍生的生物标志物应该进一步完善，它们与加速神经变性的机制联系应该被确定。应该平衡端粒修饰疗法，以最大限度地降低致癌风险，使其获益。本文综述了端粒生物学、衰老和神经系统疾病之间的因果关系，指出了端粒研究的新治疗策略和未来发展方向。

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引用次数: 0

The effects of eccentric versus traditional resistance training on muscle strength, power, hypertrophy, and functional performance in older adults: A systematic review with multilevel meta-analysis of randomized controlled trials 偏心与传统阻力训练对老年人肌肉力量、力量、肥厚和功能表现的影响：一项随机对照试验的多水平荟萃分析的系统综述。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-03 DOI: 10.1016/j.arr.2025.102933

Helmi Chaabene , Patrick Müller , Wissem Dhahbi , Karsten Königstein , Marco Taubert , Adrian Markov , Nico Lehmann

This systematic review and meta-analysis aimed to examine the effects of eccentric resistance training (ERT) versus traditional resistance training (TRT) on muscle strength, power, hypertrophy, and functional capacity in healthy older adults. Eleven randomized-controlled-trials were included. Between-group analysis for strength demonstrated a small but significant effect in favour of ERT over TRT (standardized-mean-difference [SMD]=0.27). No significant differences were found for functional capacity (SMD=0.12), muscle power (SMD=0.20), or hypertrophy (SMD=-0.03). Within-group analyses for ERT indicated large, significant effects for strength (SMD=0.96) and functional capacity (SMD=1.09) with no significant effects for power and hypertrophy. For TRT, large and moderate significant effects were found for functional capacity (SMD=0.94) and strength (SMD=0.59), respectively, with no significant effects for power and hypertrophy. Meta-regression analysis indicated that longer intervention durations were approaching-significance in their association with greater muscle strength gains with ERT than TRT (p = 0.09). With ERT, increasing age was significantly associated with greater muscle power gains (p = 0.04) and more sessions were approaching-significance in their association with hypertrophy (p = 0.08). Regarding TRT, a higher proportion of female participants was approaching-significance in its association with greater functional capacity gains (p = 0.09). In summary, ERT yields slightly greater muscle strength gains than TRT in older adults, while both produced comparable effects on functional capacity, muscle power, and hypertrophy. The two training modalities elicit moderate-to-large within-group improvements in strength and functional capacity but not in power or hypertrophy. ERT outcomes appear to be moderated by training duration, session number, and age, whereas TRT effects relate to female proportion. Overall, both modalities are effective for older adults, with a slight strength advantage for ERT.

本系统综述和荟萃分析旨在检验偏心阻力训练（ERT）与传统阻力训练（TRT）对健康老年人肌肉力量、力量、肥厚和功能能力的影响。纳入了11项随机对照试验。组间强度分析显示，ERT比TRT有小但显著的效果（标准化平均差[SMD]=0.27）。在功能容量（SMD=0.12）、肌肉力量（SMD=0.20）或肥厚（SMD=-0.03）方面没有发现显著差异。ERT的组内分析表明，力量（SMD=0.96）和功能容量（SMD=1.09）有很大的显著影响，而力量（SMD=0.85）和肥厚没有显著影响。TRT对功能容量（SMD=0.94）和力量（SMD=0.59）分别有较大和中等显著影响，对力量和肥厚没有显著影响。meta回归分析表明，与TRT相比，较长的干预时间与ERT组肌肉力量增加的相关性接近显著性（p=0.09）。对于ERT，年龄的增加与更大的肌肉力量增加显著相关（p=0.04），更多的疗程与肥厚的关联接近显著（p=0.08）。在TRT方面，女性参与者的比例越高，其与更大的功能能力增加的关联越接近显著（p=0.09）。总之，在老年人中，ERT产生的肌肉力量增益略高于TRT，而两者在功能容量、肌肉力量和肥厚方面都产生了相当的效果。这两种训练方式在力量和功能能力方面引起了中等到较大的组内改善，但在力量或肥厚方面没有改善。ERT结果似乎受训练时间、训练次数和年龄的影响，而TRT效果与女性比例有关。总的来说，这两种方式对老年人都有效，ERT有轻微的力量优势。

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引用次数: 0

AI-driven aging digital twins: A roadmap for clinical translation in precision geriatrics 人工智能驱动的老龄化数字双胞胎：精确老年医学临床翻译的路线图。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-11-03 DOI: 10.1016/j.arr.2025.102931

Chenchen Li , Ke Zuo , Ruijia Duan , Xiangbin Ouyang , Yu Zhang , Liuwang Zeng , Lite Ge

Aging and related diseases account for ⁓70 % of global mortality with declining physiological homeostasis and cognitive function increasing susceptibility to neurodegenerative disorders, cardiovascular diseases and cancer. Treatment is hampered by imprecise diagnostics and limited therapeutic options. Precision medicine involving artificial intelligence (AI)-powered Aging Digital Twin (ADT) technology which integrates multi-source heterogeneous data via advanced AI and deep learning has great potential. Virtual doppelgangers enable real-time health monitoring, predictive analytics and personalized interventions to facilitate early disease detection and optimize risk assessment and treatment strategies. Challenges remain and include age-stratified biases in training datasets and variations in data quality for older populations which may limit model generalizability. Critical concerns regarding data privacy, algorithmic transparency and clinical validation of ADT models remain unresolved. The current review examines the transformative potential of AI-enabled ADTs in precision medicine for aging and highlights technical and ethical limitations.

衰老和相关疾病占全球死亡率⁓的70%，生理稳态和认知功能下降，对神经退行性疾病、心血管疾病和癌症的易感性增加。不精确的诊断和有限的治疗选择阻碍了治疗。以人工智能（AI）为动力的老龄化数字孪生（ADT）技术，通过先进的人工智能和深度学习整合多源异构数据，具有巨大的潜力。虚拟分身能够实现实时健康监测、预测分析和个性化干预，从而促进早期疾病检测，优化风险评估和治疗策略。挑战仍然存在，包括训练数据集中的年龄分层偏差和老年人口数据质量的变化，这可能限制模型的泛化。关于数据隐私、算法透明度和ADT模型临床验证的关键问题仍未得到解决。当前的审查审查了人工智能支持的adt在老年精准医学中的变革潜力，并强调了技术和伦理限制。

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引用次数: 0

Contradictory dual role of antinutrients in nutrient inhibition and anti-aging: A comprehensive review on health benefits, processing techniques, and dietary strategies 抗营养素在营养抑制和抗衰老中的矛盾双重作用：对健康益处、加工技术和饮食策略的综合综述。

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-10-31 DOI: 10.1016/j.arr.2025.102929

Gulsah Karabulut , Deniz Günal-Köroğlu , Hilal Yılmaz , Ezgi Erskine , Esra Capanoglu

Background

Antinutritional factors (antinutrients) are bioactive compounds in plant-derived foods that can impair nutrient absorption and reduce the bioavailability of proteins, carbohydrates, and essential minerals. Major representatives include phytates, oxalates, lectins, tannins, saponins, and enzyme inhibitors, which are associated with adverse nutritional outcomes through interference with nutrient uptake.

Scope and approach

Recent studies reveal that antinutrients also possess bioactive properties with potential benefits for aging and longevity. This review assesses their dual role, considering both their inhibitory effects on nutrient utilization and their emerging therapeutic potential, and discusses dietary strategies and processing techniques that minimize risks while enhancing health-promoting properties.

Key findings and conclusions

Aging is driven by oxidative stress, inflammation, mitochondrial dysfunction, and cellular senescence, all of which contribute to cancer, cardiovascular disease, and neurodegeneration. Antinutrients may counteract these processes via antioxidant, anti-inflammatory, and autophagy-modulating actions. For instance, phytates protect against oxidative damage, saponins support mitochondrial function, and processing methods such as fermentation, soaking, and germination can reduce harmful effects while preserving bioactivity. Understanding these interactions highlights opportunities to harness antinutrients as functional compounds to promote healthy aging and extend healthspan.

背景：抗营养因子（抗营养素）是植物源性食物中的生物活性化合物，可损害营养吸收，降低蛋白质、碳水化合物和必需矿物质的生物利用度。主要代表包括植酸盐、草酸盐、凝集素、单宁酸、皂苷和酶抑制剂，它们通过干扰营养摄取而与不良营养结果相关。范围和方法：最近的研究表明，抗营养素还具有生物活性特性，对衰老和长寿有潜在的好处。这篇综述评估了它们的双重作用，考虑了对营养利用的抑制作用和新兴的治疗潜力，并讨论了饮食策略和加工技术，以最大限度地降低风险，同时增强健康促进特性。主要发现和结论：衰老是由氧化应激、炎症、线粒体功能障碍和细胞衰老驱动的，导致癌症、心血管疾病和神经变性。抗营养物质可以通过抗氧化、抗炎和自噬调节作用来抵消这些过程。例如，植酸盐可以防止氧化损伤，皂苷支持线粒体功能，发酵、浸泡和发芽等加工方法可以在保持生物活性的同时减少有害影响。了解这些相互作用凸显了利用抗营养素作为促进健康衰老和延长健康寿命的功能性化合物的机会。

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引用次数: 0

Three-dimensional human brain organoids: A next-generation model to decode Alzheimer’s disease 三维人脑类器官：解码阿尔茨海默病的下一代模型

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews

Pub Date : 2025-10-24 DOI: 10.1016/j.arr.2025.102928

Sneha Kumari , Ashvin , Rishika Dhapola , Prajjwal Sharma , Mohit Paidlewar , Balachandar Vellingiri , Bikash Medhi , Dibbanti HariKrishnaReddy

Brain organoids are an emerging in vitro three-dimensional (3D) brain model derived from pluripotent stem cells. This model emulates the developmental processes of the human brain and associated disease phenotypes to some degree, while facilitating the advancement into human brain-inspired biological intelligence. This review highlights the evolution of brain organoid technology from conventional 2D cultures to advanced 3D models, emphasizing methodological innovations such as guided differentiation, bioengineering, and patient-derived induced pluripotent stem cells (iPSCs). We focus on their applications in Alzheimer’s disease (AD), including elucidation of disease pathophysiology, modeling of amyloid-β and tau pathology, investigation of neuroinflammatory and blood-brain barrier (BBB) dysfunction, and their utility in drug screening and describe the diverse categories of brain organoids, including neural organoids, neuroimmune organoids, myelinoids, BBB organoids, and choroid plexus organoids. We discuss key technological advancements, guided differentiation, bioengineering approaches, microfluidic systems, and assembloid strategies that enhance cellular diversity, maturation, and functional relevance. Furthermore, we discuss therapeutic insights gained from organoid-based studies, current limitations such as incomplete maturation and vascularization, and future directions involving immune cell integration, vascularized models, and AI-driven analysis. We have also discussed some current drug screening and therapeutic development for AD using brain organoids. Together, this review provides a comprehensive perspective on the potential of brain organoids as powerful platforms for advancing AD research and accelerating therapeutic discovery.

脑类器官是一种新兴的体外三维（3D）脑模型，来源于多能干细胞。该模型在一定程度上模拟了人类大脑的发育过程和相关的疾病表型，同时促进了人类大脑启发生物智能的进展。这篇综述强调了脑类器官技术从传统的2D培养到先进的3D模型的演变，强调了方法上的创新，如引导分化、生物工程和患者来源的诱导多能干细胞（iPSCs）。我们关注它们在阿尔茨海默病（AD）中的应用，包括疾病病理生理学的阐明，淀粉样蛋白-β和tau病理学的建模，神经炎症和血脑屏障（BBB）功能障碍的研究，以及它们在药物筛选中的应用，并描述了脑类器官的不同类别，包括神经类器官，神经免疫类器官，髓鞘类器官，血脑屏障类器官和脉络膜丛类器官。我们讨论了关键的技术进步，引导分化，生物工程方法，微流体系统和组装体策略，增强细胞多样性，成熟和功能相关性。此外，我们还讨论了从基于类器官的研究中获得的治疗见解，当前的局限性，如不完全成熟和血管化，以及涉及免疫细胞整合、血管化模型和人工智能驱动分析的未来方向。我们还讨论了一些目前的药物筛选和利用脑类器官治疗阿尔茨海默病的发展。总之，这篇综述提供了一个全面的视角，即脑类器官作为推进AD研究和加速治疗发现的强大平台的潜力。

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引用次数: 0