Title

Mdm2-p53 signaling regulates epidermal stem cell senescence and premature aging phenotypes in mouse skin

UMMS Affiliation

Department of Cell Biology; Department of Cancer Biology

Date

5-1-2011

Document Type

Article

Subjects

Cell Aging; Epidermis; Proto-Oncogene Proteins c-mdm2; Signal Transduction; Skin Aging; Stem Cells; Tumor Suppressor Protein p53

Abstract

The p53 transcription factor is activated by various types of cell stress or DNA damage and induces the expression of genes that control cell growth and inhibit tumor formation. Analysis of mice that express mutant forms of p53 suggest that inappropriate p53 activation can alter tissue homeostasis and life span, connecting p53 tumor suppressor functions with accelerated aging. However, other mouse models that display increased levels of wildtype p53 in various tissues fail to corroborate a link between p53 and aging phenotypes, possibly due to the retention of signaling pathways that negatively regulate p53 activity in these models. In this present study, we have generated mice lacking Mdm2 in the epidermis. Deletion of Mdm2, the chief negative regulator of p53, induced an aging phenotype in the skin of mice, including thinning of the epidermis, reduced wound healing, and a progressive loss of fur. These phenotypes arise due to an induction of p53-mediated senescence in epidermal stem cells and a gradual loss of epidermal stem cell function. These results reveal that activation of endogenous p53 by ablation of Mdm2 can induce accelerated aging phenotypes in mice.

Rights and Permissions

Citation: Dev Biol. 2011 May 1;353(1):1-9. Epub 2011 Feb 17. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Developmental biology

PubMed ID

21334322