Selenium and brain aging: A comprehensive review with a focus on hippocampal neurogenesis

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-09-12 DOI:10.1016/j.arr.2025.102898

Arian Daneshpour , Maria Eduarda Nastarino Leite , Karl-Heinz Wagner , Shaun Sabico , Nasser M. Al-Daghri , Dara Aldisi , Daniel König , José Francisco López Gil , Brendon Stubbs

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Abstract

Brain aging is accompanied by progressive cognitive decline and increased risk of neurodegenerative diseases, with adult hippocampal neurogenesis (AHN) playing a pivotal role in maintaining cognitive resilience. Selenium, an essential trace element, exerts significant neuroprotective and neurogenic effects predominantly through its incorporation into selenoproteins, which regulate oxidative stress, neuroinflammation, and synaptic plasticity. This review synthesizes recent advances delineating selenium’s metabolism, bioavailability, and its multifaceted roles in brain development, function, and aging, emphasizing mechanisms underpinning hippocampal neurogenesis. Key molecular pathways influenced by selenium include phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Wingless/Integrated (Wnt) and brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathways that promote neural progenitor cell proliferation and differentiation. Selenium transport via selenoprotein P and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) is critical for adequate selenium delivery to the hippocampus to support neurogenesis, with exercise demonstrated to potentiate this axis. Selenium also mitigates ferroptosis, preserves mitochondrial integrity, and modulates neuroimmune interactions by attenuating microglial activation and inflammasome signaling, fostering a neurogenic environment. Emerging evidence highlights selenium’s regulatory effects on RNA expression, including microRNAs modifications, further influencing neuronal health. Despite promising preclinical and observational data, clinical translation remains limited by heterogeneous and short-term studies. Future research priorities include multi-omics investigations, longitudinal cohorts, and addressing global selenium intake disparities through policy initiatives and precision nutrition. By consolidating mechanistic insights with clinical perspectives, this review underscores selenium’s potential as a modifiable factor to enhance AHN and cognitive health, advocating for integrated translational strategies to combat brain aging and neurodegeneration.

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硒与脑衰老：以海马神经发生为重点的综合综述。

脑老化伴随着进行性认知能力下降和神经退行性疾病的风险增加，成人海马神经发生（AHN）在维持认知弹性方面起着关键作用。硒是一种必需的微量元素，主要通过与硒蛋白结合发挥重要的神经保护和神经原性作用，硒蛋白调节氧化应激、神经炎症和突触可塑性。本文综述了硒的代谢、生物利用度及其在大脑发育、功能和衰老中的多方面作用的最新进展，重点介绍了海马神经发生的机制。受硒影响的关键分子通路包括促进神经祖细胞增殖和分化的磷酸肌苷3激酶(PI3K)/蛋白激酶B (Akt)/无翼/集成（Wnt）和脑源性神经营养因子(BDNF)/原肌球蛋白受体激酶B （TrkB）信号通路。硒通过硒蛋白P及其受体低密度脂蛋白受体相关蛋白8 （LRP8）运输，对于将足够的硒输送到海马体以支持神经发生至关重要，而运动已被证明可以增强这一轴。硒还可以减轻铁凋亡，保持线粒体完整性，并通过减弱小胶质细胞激活和炎性小体信号调节神经免疫相互作用，促进神经源性环境。新出现的证据强调硒对RNA表达的调节作用，包括微小RNA修饰，进一步影响神经元健康。尽管临床前和观察数据很有希望，但临床转化仍然受到异质性和短期研究的限制。未来的研究重点包括多组学调查、纵向队列研究，以及通过政策举措和精确营养来解决全球硒摄入差异。通过将机制见解与临床观点相结合，本综述强调了硒作为增强AHN和认知健康的可调节因素的潜力，并倡导了对抗脑衰老和神经变性的综合转化策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.