{"title":"Gastrointestinal redox homeostasis in ageing.","authors":"Jan Homolak","doi":"10.1007/s10522-023-10049-8","DOIUrl":null,"url":null,"abstract":"<p><p>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 H<sub>2</sub>O<sub>2</sub> 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.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"24 5","pages":"741-752"},"PeriodicalIF":4.4000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-023-10049-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.