Gastrointestinal redox homeostasis in ageing.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2023-10-01 Epub Date: 2023-07-12 DOI:10.1007/s10522-023-10049-8
Jan Homolak
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Abstract

The gastrointestinal (GI) barrier acts as the primary interface between humans and the external environment. It constantly faces the risk of inflammation and oxidative stress due to exposure to foreign substances and microorganisms. Thus, maintaining the structural and functional integrity of the GI barrier is crucial for overall well-being, as it helps prevent systemic inflammation and oxidative stress, which are major contributors to age-related diseases. A healthy gut relies on maintaining gut redox homeostasis, which involves several essential elements. Firstly, it requires establishing a baseline electrophilic tone and an electrophilic mucosal gradient. Secondly, the electrophilic system needs to have sufficient capacity to generate reactive oxygen species, enabling effective elimination of invading microorganisms and rapid restoration of the barrier integrity following breaches. These elements depend on physiological redox signaling mediated by electrophilic pathways such as NOX2 and the H2O2 pathway. Additionally, the nucleophilic arm of redox homeostasis should exhibit sufficient reactivity to restore the redox balance after an electrophilic surge. Factors contributing to the nucleophilic arm include the availability of reductive substrates and redox signaling mediated by the cytoprotective Keap1-Nrf2 pathway. Future research should focus on identifying preventive and therapeutic strategies that enhance the strength and responsiveness of GI redox homeostasis. These strategies aim to reduce the vulnerability of the gut to harmful stimuli and address the decline in reactivity often observed during the aging process. By strengthening GI redox homeostasis, we can potentially mitigate the risks associated with age-related gut dyshomeostasis and optimize overall health and longevity.

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衰老过程中胃肠道氧化还原稳态。
胃肠道屏障是人类与外部环境之间的主要界面。由于接触外来物质和微生物,它不断面临炎症和氧化应激的风险。因此,保持胃肠道屏障的结构和功能完整性对整体健康至关重要,因为它有助于预防全身炎症和氧化应激,而这些是导致年龄相关疾病的主要因素。健康的肠道依赖于维持肠道氧化还原稳态,这涉及到几个基本元素。首先,它需要建立一个基线亲电色调和亲电粘膜梯度。其次,亲电系统需要有足够的能力产生活性氧,从而能够有效消除入侵的微生物,并在破坏后快速恢复屏障的完整性。这些元素依赖于由亲电途径如NOX2和H2O2途径介导的生理氧化还原信号传导。此外,氧化还原稳态的亲核臂应表现出足够的反应性,以在亲电浪涌后恢复氧化还原平衡。有助于亲核臂的因素包括还原底物的可用性和细胞保护性Keap1-Nrf2途径介导的氧化还原信号传导。未来的研究应侧重于确定预防和治疗策略,以增强胃肠道氧化还原稳态的强度和反应性。这些策略旨在降低肠道对有害刺激的脆弱性,并解决衰老过程中经常观察到的反应性下降问题。通过加强胃肠道氧化还原稳态,我们可以潜在地减轻与年龄相关的肠道稳态失调的风险,并优化整体健康和寿命。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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