单核细胞驱动的炎症老化会降低女性的肠道屏障功能。

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2024-09-30 DOI:10.1186/s12979-024-00469-6
Candice Quin, Jessica A Breznik, Allison E Kennedy, Erica N DeJong, Catherine M Andary, Sofya Ermolina, Donald J Davidson, Jinhui Ma, Michael G Surette, Dawn M E Bowdish
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引用次数: 0

摘要

背景:肠道屏障包括物理和免疫成分,这些成分的作用是将肠腔内容物(如细菌和内毒素)与宿主隔离开来。有人提出,与年龄有关的肠道屏障功能下降可能使肠腔内容物进入血液,引发低度全身性炎症,即炎症老化。尽管有越来越多的证据支持在模式物种中的这一假设,但目前还不清楚这一现象是否发生在人类身上。此外,尽管生物性别对衰老生理的影响已得到证实,但其对肠道屏障功能和炎症衰老的影响尚未得到探讨:在这项研究中,我们观察到肠道屏障完整性标志物的性别差异。随着年龄的增长,女性体内循环细菌产物和代谢物(如 LPS 和犬尿氨酸)的增加与年龄有关,这表明女性的屏障功能降低了。女性的炎症老化标志物(包括外周血单核细胞以及 TNF 和 CRP)也随着年龄的增长而增加。为了确定屏障功能受损是否是炎症老化的驱动因素,我们进行了一项中介分析。结果显示,肠道屏障完整性的丧失并不是人类炎症老化的中介因素。相反,随着年龄的增长,持续的低度炎症会先于循环细菌产物的增加,我们利用动物模型证实了这一点。我们发现,与人类一样,性别也会改变小鼠循环单核细胞随年龄增长而增加的情况,而且炎症会介导肠道屏障功能的丧失:综上所述,我们的研究结果表明,较高的基础肠道通透性与年龄相关性炎症相结合,会增加雌性小鼠体内的循环 LPS。因此,针对雌性肠道屏障的渗透性可能会减缓炎症老化的进程,但不太可能预防炎症老化。
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Monocyte-driven inflamm-aging reduces intestinal barrier function in females.

Background: The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans. In addition, despite being well-established that biological sex impacts aging physiology, its influence on intestinal barrier function and inflamm-aging has not been explored.

Results: In this study, we observed sex differences in markers of intestinal barrier integrity, where females had increased epithelial permeability throughout life as compared to males. With age, females had an age-associated increase in circulating bacterial products and metabolites such as LPS and kynurenine, suggesting reduced barrier function. Females also had age-associated increases in established markers of inflamm-aging, including peripheral blood monocytes as well as TNF and CRP. To determine if impaired barrier function was driving inflamm-aging, we performed a mediation analysis. The results show that the loss of intestinal barrier integrity was not the mediator of inflamm-aging in humans. Instead, persistent, low-grade inflammation with age preceded the increase in circulating bacterial products, which we confirmed using animal models. We found, as in humans, that sex modified age-associated increases in circulating monocytes in mice, and that inflammation mediates the loss of intestinal barrier function.

Conclusion: Taken together, our results suggest that higher basal intestinal permeability in combination with age-associated inflammation, increases circulating LPS in females. Thus, targeting barrier permeability in females may slow the progression of inflamm-aging, but is unlikely to prevent it.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
期刊最新文献
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