Genotype Frequencies Alcohol Cirrhosis vs Control   AA AG GG P value Alcohol Cirrhosis (n=34) 0 (0%) 9 (26.5%) 25 (73.53%)   Control (n= 161) 1 (0.62′/;) 14(8.7%) 146(90.68%) Disclosures: The following people have nothing to disclose: Alison Jazwinski, Nijole Pollock, Kimberly Stello, Michael O’Connell, David C. Whitcomb Chronic alcohol consumption is a leading cause of chronic liver disease with broad spectrum of disorders including: fatty liver, steatohepatitis, cirrhosis, selleck products and hepatocellular carcinoma. Accumulating evidence suggests that elderly people have more severe liver injury after excessive drinking than young people, but the underlying mechanisms are not clear. In the current study, 2-, 12-, and 18-month

old female C57BL/6J mice were subjected to 10-day chronic plus single binge feeding (NIAAA model). Twelve- and 18-month old mice had higher levels

of serum ALT and AST compared with 2-month old mice. Liver his-tological analysis revealed that there was greater degree of steatosis and bigger lipid droplets in the liver from ethanol-fed old mice than those from young mice. Hepatic expressions of several pro-inflammatory genes and CYP2E1 protein were comparable in ethanol-fed young and old mice. Interestingly, chronic plus binge ethanol BGB324 order feeding markedly increased autophagy in the liver in young mice, but to a lesser extent in old mice. Hepatic expression of Sirtuin 1 (Sirt 1) was markedly lower in old mice compared to young mice. Chronic plus binge ethanol feeding upregulated hepatic Sirt1 expression with two fold higher in young mice than in old mice. In vitro exposure of ethanol induced autophagosome in hepatocytes from young mice, but such induction was much weaker in hepatocytes from old mice. Overexpression of Sirt1 via the infection of aden-ovirus Sirt1 restored ethanol-induced autophagosome in these old mouse many hepatocytes. These findings suggest that aging downregulates hepatic Sirt1 protein expression

and consequently inhibits autophagy, thereby exacerbating alcoholic liver injury. Disclosures: The following people have nothing to disclose: Yongmei Li, Dechun Feng, Ming-Jiang Xu, Hua Wang, Yan Wang, Bin Gao Purpose: Alcohol is the most socially accepted addictive drug, and it can cause liver disease, which is a major cause of morbidity and mortality in the United States. Animal and human studies demonstrate that chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Also, acrolein is a major component of cigarette smoke, and there is increasing evidence that smoking negatively impacts the incidence, severity, and clinical course of chronic liver disease. Acrolein is known to form DNA and protein adducts, and can trigger endoplasmic reticulum (ER) stress. Notably, alcohol-induced perturbations in the ER have emerged as an important etiologic factor in alcoholic liver disease.