Effect of aging on the development and progression of alcohol-associated liver disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our findings indicate that aging significantly influences the development of liver injury after chronic alcohol intake.