NIH Research Festival
FARE Award Winner
Alcoholic liver disease (ALD), one of the most prevalent forms of liver disease worldwide, is often caused by excessive alcohol consumption. The mechanisms by which chronic ethanol consumption and aging play a role in ALD remain unclear. We hypothesized that aging may have an interaction effect with ethanol exposure that may play a role in down-regulating hepatic SIRT1 protein expression, inducing liver injury and fibrosis. For our studies, C57BL/6 mice were first acclimatized to control liquid diets for 5 days. Then, they were chronically fed with control or liquid diets containing 5% (v/v) ethanol for 10 days, followed by a single ethanol binge (5g/kg body weight) or fed up to 8 weeks, which included multiple binges of ethanol. The results from liver histological analysis from a single binge revealed that there was a greater degree of steatosis and reduced hepatic protein levels of SIRT1 in the livers from ethanol-fed old mice when compared to young mice. Chronic multiple binge ethanol exposed old mice demonstrated more steatosis, neutrophil infiltration and fibrosis when compared to young mice, correlating to the characteristics of ALD. The current results suggest that aging plays a role in down-regulating hepatic SIRT1 protein expression in hepatocytes in old mice, consequently inducing alcoholic liver injury and fibrosis. These novel findings will help us to better understand the importance of how aging and alcohol induced liver injury greatly affects the elderly population, and develop ways to help prevent further injury.
Scientific Focus Area: Molecular Pharmacology
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