There are currently > 600 million people over the age of 65 globally and this number is expected to double by the year 2050. Alcohol use among this population is on the rise, which is concerning as aging is associated with increased risk for a number of chronic illnesses. As most studies investigating the effects of alcohol have focused on young/middle-aged populations, there is a dearth of information regarding the consequences of alcohol use in older consumers. In addition, most murine ethanol models have concentrated on exposure to very high levels of ethanol, while the vast majority of elderly drinkers do not consume alcohol in excess; instead, they drink on average 2 alcoholic beverages a day, 3–4 days a week. We designed a murine model of aging and moderate ethanol consumption to determine if the deleterious effects of alcohol on the gut-liver axis are exacerbated in aged, relative to younger, animals. Aged and young mice were exposed to a multi-day moderate exposure ethanol regimen for 4 weeks and changes in gut permeability along with intestinal tight junction protein and antimicrobial peptide gene expression were measured. In addition, hepatic inflammation was assessed by histological analysis, inflammatory gene expression and flow cytometric analysis of inflammatory infiltrate. Our results reveal that in aged, but not young mice, moderate ethanol exposure yielded significantly worsened intestinal permeability, including increased bacterial translocation from the gut, elevated serum iFABP and leakage of FITC-dextran from the gut. Interestingly, moderate ethanol exposure in young animals led to gut protective transcriptional changes in the ileum while this protective response was blunted in aged mice. Finally, moderate ethanol exposure in aged mice also resulted in marked inflammatory changes in the liver. These results demonstrate that aged mice are more susceptible to ethanol-induced gut barrier dysfunction and liver inflammation, even at moderate doses of ethanol. This increased vulnerability to ethanol’s gastrointestinal effects has important implications for alcohol use in the aging population. Future studies will explore whether improving intestinal barrier function can reverse these age-related changes.

中文翻译：

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一种新的多日适度乙醇暴露小鼠模型显示，随着年龄的增长，肠道功能障碍和肝脏炎症增加

目前全球 65 岁以上的人口超过 6 亿，预计到 2050 年这一数字将翻一番。这一人群的酒精使用量正在上升，这令人担忧，因为老龄化与一些慢性病风险增加有关疾病。由于大多数调查酒精影响的研究都集中在年轻/中年人群，因此缺乏关于老年消费者饮酒后果的信息。此外，大多数小鼠乙醇模型都集中于暴露于非常高水平的乙醇，而绝大多数老年饮酒者并没有过量饮酒；相反，他们平均每天喝 2 杯酒精饮料，每周 3-4 天。我们设计了一个老化和适度饮酒的小鼠模型，以确定酒精对肠-肝轴的有害影响是否会在老年动物（相对于年轻动物）中加剧。将老年和年轻小鼠暴露于为期 4 周的多天适度暴露乙醇方案中，并测量肠道通透性以及肠道紧密连接蛋白和抗菌肽基因表达的变化。此外，通过组织学分析、炎症基因表达和炎症浸润的流式细胞术分析评估肝脏炎症。我们的研究结果表明，在老年而非年轻小鼠中，适度的乙醇暴露导致肠道通透性显着恶化，包括肠道细菌易位增加、血清 iFABP 升高和 FITC-葡聚糖从肠道渗漏。有趣的是，年幼动物中度乙醇暴露导致回肠的肠道保护性转录变化，而这种保护性反应在老年小鼠中减弱。最后，老年小鼠中度乙醇暴露也会导致肝脏出现明显的炎症变化。这些结果表明，即使在中等剂量的乙醇下，老年小鼠也更容易受到乙醇引起的肠道屏障功能障碍和肝脏炎症的影响。这种对乙醇胃肠道影响的脆弱性增加对老年人口中的酒精使用具有重要意义。未来的研究将探索改善肠道屏障功能是否可以逆转这些与年龄相关的变化。老年小鼠中度乙醇暴露也会导致肝脏出现明显的炎症变化。这些结果表明，即使在中等剂量的乙醇下，老年小鼠也更容易受到乙醇引起的肠道屏障功能障碍和肝脏炎症的影响。这种对乙醇胃肠道影响的脆弱性增加对老年人口中的酒精使用具有重要意义。未来的研究将探索改善肠道屏障功能是否可以逆转这些与年龄相关的变化。老年小鼠中度乙醇暴露也会导致肝脏出现明显的炎症变化。这些结果表明，即使在中等剂量的乙醇下，老年小鼠也更容易受到乙醇引起的肠道屏障功能障碍和肝脏炎症的影响。这种对乙醇胃肠道影响的脆弱性增加对老年人口中的酒精使用具有重要意义。未来的研究将探索改善肠道屏障功能是否可以逆转这些与年龄相关的变化。这种对乙醇胃肠道影响的脆弱性增加对老年人口中的酒精使用具有重要意义。未来的研究将探索改善肠道屏障功能是否可以逆转这些与年龄相关的变化。这种对乙醇胃肠道影响的脆弱性增加对老年人口中的酒精使用具有重要意义。未来的研究将探索改善肠道屏障功能是否可以逆转这些与年龄相关的变化。