Document Detail


p63 deficiency activates a program of cellular senescence and leads to accelerated aging.
MedLine Citation:
PMID:  16107615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
William M Keyes; Ying Wu; Hannes Vogel; Xuecui Guo; Scott W Lowe; Alea A Mills
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-08-17
Journal Detail:
Title:  Genes & development     Volume:  19     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-10-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1986-99     Citation Subset:  IM    
Affiliation:
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
AR47898/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Phosphoproteins; 0/Trans-Activators; 0/Trp63 protein, mouse; 0/Tumor Suppressor Proteins
Comments/Corrections

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