LAUSR

SELECTION OF THE MONTH Aging increases risk of alcohol-related liver fibrosis An intriguing paper in this issue investigates the mechanisms by which aging exacerbates the progression of alcoholic liver disease (ALD). Ramirez el al. demonstrate that, compared to young mice, middle-aged and old mice are more susceptible to alcoholinduced liver injury. Importantly, restoring hepatic expression of sirtuin 1 (Gene Symbol: Sirt1), which is markedly lower in older mice, ameliorates subacute liver injury induced by alcohol and also improves the fibrogenic response to chronic liver injury. A role for Sirt1 in mediating the effects of aging in experimental ALD was confirmed in Sirt1-deficient mice. These intriguing results were confirmed at the cellular level, since hepatic stellate cells from older mice express lower levels of the Sirt1 gene product, which regulates their profibrogenic actions. This important study shows that aging exacerbates ALD in mice through the downregulation of Sirt1 in the liver. Alcohol + Aging