DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse.
Publication/Presentation Date
9-1-2006
Abstract
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 deltaNp63alpha 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 deltaNp63alpha 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 deltaNp63alpha expression induced cellular senescence that was rescued by Sirt1. Our data suggest that deltaNp63alpha levels may affect aging in mammals, at least in part, through regulation of Sirt1.
Volume
5
Issue
17
First Page
2005
Last Page
2011
ISSN
1551-4005
Published In/Presented At
Sommer, M., Poliak, N., Upadhyay, S., Ratovitski, E., Nelkin, B. D., Donehower, L. A., & Sidransky, D. (2006). DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell cycle (Georgetown, Tex.), 5(17), 2005–2011. https://doi.org/10.4161/cc.5.17.3194
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
16940753
Department(s)
Department of Pediatrics
Document Type
Article