Effects of age and gender on Sirt 1 mRNA expressions in the hypothalamus of the mouse.

Sirt1 is a NAD-dependent deacetylase that has been shown as a link between energy metabolism and aging. Its putative role as a target for neurodegenerative disorders has recently been suggested; yet, little is known about the changes that occur in Sirt1 levels in the aging brain. Here we show by in situ hybridization that Sirt1 expression is modified in specific areas of the brain in mice upon aging, and that gender also impacts on this regulation. Mice aged 12 and 24 months had a lower Sirt1 expression specifically in the antero ventral thalamic nucleus (AV) and in the arcuate nucleus (ARC) than their young (4mo) counterparts, whereas changes were either not noticeable or not significantly modulated in other parts of the brain. Regulation of Sirt1 mRNA levels in the subfornical organ (SFO) and in the substancia nigra part compacta (SNC) depended on gender. These findings suggest that reduced Sirt1 levels upon aging could contribute to a lower Sirt1 activity, and that specific nuclei might be particularly affected.