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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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: | https://repository.cshl.edu/id/eprint/22619 |
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