ΔNp63α 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, David Sidransky

Research output: Contribution to journalArticle

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 ΔNp63α 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 ΔNp63α 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 ΔNp63α expression induced cellular senescence that was rescued by Sirt1. Our data suggest that ΔNp63α levels may affect aging in mammals, at least in part, through regulation of Sirt1.

Original languageEnglish (US)
Pages (from-to)2005-2011
Number of pages7
JournalCell cycle (Georgetown, Tex.)
Volume5
Issue number17
StatePublished - Sep 1 2006

Fingerprint

Skin
Down-Regulation
Aging of materials
Phenotype
Transgenic Mice
Skin Aging
Cell Aging
Subcutaneous Fat
Differentiation Antigens
Alopecia
Subcutaneous Tissue
Keratinocytes
Mammals
Wound Healing
Cell proliferation
Cell Proliferation
Fats
Tissue
Defects

Keywords

  • Aging
  • p53
  • p63
  • Sirt1
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology
  • Medicine(all)

Cite this

ΔNp63α overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. / Sommer, Matthias; Poliak, Nina; Upadhyay, Sunil; Ratovitski, Edward; Nelkin, Barry D; Donehower, Lawrence A.; Sidransky, David.

In: Cell cycle (Georgetown, Tex.), Vol. 5, No. 17, 01.09.2006, p. 2005-2011.

Research output: Contribution to journalArticle

Sommer, M, Poliak, N, Upadhyay, S, Ratovitski, E, Nelkin, BD, Donehower, LA & Sidransky, D 2006, 'ΔNp63α overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse', Cell cycle (Georgetown, Tex.), vol. 5, no. 17, pp. 2005-2011.
Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, Donehower LA et al. ΔNp63α overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell cycle (Georgetown, Tex.). 2006 Sep 1;5(17):2005-2011.
Sommer, Matthias ; Poliak, Nina ; Upadhyay, Sunil ; Ratovitski, Edward ; Nelkin, Barry D ; Donehower, Lawrence A. ; Sidransky, David. / ΔNp63α overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. In: Cell cycle (Georgetown, Tex.). 2006 ; Vol. 5, No. 17. pp. 2005-2011.
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