Bellamkonda Ramesh, Mahalingam Sundararajan, Ethiraj Ojeshvi, Perumal Sathish Kumar, Arumugam Madan Kumar, Knoell Daren L, Fisher Kurt W, Casey Carol A, Kharbanda Kusum K, Rasineni Karuna
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Jul;49(7):1412-1423. doi: 10.1111/acer.70086. Epub 2025 Jun 3.
There is a robust link between chronic alcohol intake and the development of alcohol-associated liver disease (ALD). Over 90% of excessive alcohol drinkers develop hepatic steatosis that can progress to an advanced liver injury state. However, this progression depends on many extrahepatic factors including age, which is also a predictor of ALD-related mortality. This study aimed to identify selected pathological changes in rats of different ages with chronic ethanol administration for the same duration to gain insights into the effects of aging in the development and progression of ALD.
Male Wistar rats of young (4 months), middle (8-12 months), and older (24 months) age were pair-fed for 6 weeks with Lieber-DeCarli control or ethanol diet. At the end of the experimental period, rats were euthanized and serum and tissues (liver, gut, and adipose) were collected for analyses.
Chronic ethanol feeding increased serum hepatic injury markers, circulating nonesterified free fatty acids, and hepatic triglycerides across the different age groups compared to their respective controls, with the higher levels seen in the middle-aged and old ethanol-fed rats compared to young ethanol-fed rats. Further, histopathological evaluation and quantitative analysis of inflammatory and fibrotic markers revealed more progressive liver injury in older ethanol-fed rats compared to young and middle-aged counterparts. We also observed increased intestinal permeability, as indicated by lower ileal expression of tight junction proteins and higher serum endotoxin levels in older ethanol-fed rats. Aging alone adversely affected several of these injury markers in older control-fed rats compared to middle-aged and young control-fed rats.
Our findings indicate that aging significantly influences the development of liver injury after chronic alcohol intake.
长期饮酒与酒精性肝病（ALD）的发生之间存在密切联系。超过90%的过量饮酒者会出现肝脂肪变性，进而可能发展为严重的肝损伤状态。然而，这种进展取决于许多肝外因素，包括年龄，年龄也是ALD相关死亡率的一个预测指标。本研究旨在确定在相同时间段内长期给予乙醇的不同年龄大鼠的某些病理变化，以深入了解衰老在ALD发生和发展中的作用。
将年轻（4个月）、中年（8 - 12个月）和老年（24个月）的雄性Wistar大鼠分别与Lieber - DeCarli对照饲料或乙醇饲料配对喂养6周。实验期结束时，对大鼠实施安乐死，并收集血清和组织（肝脏、肠道和脂肪组织）进行分析。
与各自的对照组相比，长期给予乙醇使不同年龄组大鼠的血清肝损伤标志物、循环中非酯化游离脂肪酸和肝脏甘油三酯水平升高，中年和老年乙醇喂养大鼠的这些指标水平高于年轻乙醇喂养大鼠。此外，组织病理学评估以及炎症和纤维化标志物的定量分析显示，老年乙醇喂养大鼠的肝损伤比年轻和中年大鼠更严重。我们还观察到老年乙醇喂养大鼠的肠道通透性增加，表现为回肠紧密连接蛋白表达降低和血清内毒素水平升高。与中年和年轻对照喂养大鼠相比，仅衰老就对老年对照喂养大鼠的一些损伤标志物产生了不利影响。
我们的研究结果表明，衰老显著影响长期饮酒后肝损伤的发生。
