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ΔNp63&alpha Overexpression Induces Downregulation of Sirt1 and an Accelerated Aging Phenotype in the Mouse
Matthias Sommer, Nina Poliak, Sunil Upadhyay, Edward Ratovitski, Barry D. Nelkin, Lawrence A Donehower and David Sidransky
volume 5 | issue 17
1 september 2006Pages: 2005 - 2011
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p63 is highly expressed in the skin and appears to be an early marker of keratinocyte differentiation. To examine the role of p63 in vivo, we generated transgenic mice that overexpress ΔNp63&alpha in the skin. These mice exhibited an accelerated aging phenotype in the skin characterized by striking wound healing defects, decreased skin thickness, decreased subcutaneous fat tissue, hair loss, and decreased cell proliferation. The accelerated skin aging was accompanied by a dramatic decrease in longevity of the mice. We found that aging in ΔNp63&alpha transgenic mice and other mouse models correlated with levels of Sirt1, a mammalian SIR2 orthologue thought to extend the lifespan in lower species. Moreover, increased ΔNp63&alpha expression induced cellular senescence that was rescued by Sirt1. Our data suggest that ΔNp63&alpha levels may affect aging in mammals, at least in part, through regulation of Sirt1.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.