p63 deficiency activates a program of cellular senescence and leads to accelerated aging
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 wi...
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Published in | Genes & development Vol. 19; no. 17; pp. 1986 - 1999 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
01.09.2005
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 E-MAIL mills@cshl.edu ; FAX (516) 367-8874. Supplemental material is available at http://www.genesdev.org. Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.342305. Corresponding author. |
ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.342305 |