p63 deficiency activates a program of cellular senescence and leads to accelerated aging

Keyes, William M., Wu, Ying, Vogel, Hannes, Guo, Xuecui, Lowe, Scott W., Mills, Alea A. (September 2005) p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev, 19 (17). pp. 1986-99. ISSN 0890-9369 (Print)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/16107615
DOI: 10.1101/gad.342305

Abstract

The p53 tumor suppressor plays a key role in organismal aging. A cellular mechanism postulated to drive the aging process is cellular senescence, mediated in part by p53. Although senescent cells accumulate in elderly individuals, most studies have relied on correlating in vitro senescence assays with in vivo phenotypes of aging. Here, using two different mouse models in which the p53-related protein p63 is compromised, we demonstrate that cellular senescence and organismal aging are intimately linked and that these processes are mediated by p63 loss. We found that p63(+/-) mice have a shortened life span and display features of accelerated aging. Both germline and somatically induced p63 deficiency activates widespread cellular senescence with enhanced expression of senescent markers SA-beta-gal, PML, and p16(INK4a). Using an inducible tissue-specific p63 conditional model, we further show that p63 deficiency induces cellular senescence and causes accelerated aging phenotypes in the adult. Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process.

Item Type: Paper
Uncontrolled Keywords: Aging genetics physiology Aging Premature etiology genetics pathology Animals Base Sequence Cell Aging genetics physiology Cells Cultured DNA Complementary genetics Epithelium pathology Female Keratinocytes pathology Male Mice Mice Mutant Strains Mice Transgenic Phenotype Phosphoproteins deficiency genetics physiology Pregnancy Trans-Activators deficiency genetics physiology Tumor Suppressor Proteins deficiency genetics physiology
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p63
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL labs > Mills lab
Depositing User: CSHL Librarian
Date: 1 September 2005
Date Deposited: 12 Jan 2012 16:46
Last Modified: 02 Feb 2017 19:56
PMCID: PMC1199570
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22619

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