The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
p63 deficiency activates a program of cellular senescence and leads to accelerated aging
Open accessAbstract
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-β-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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Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
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Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
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BackgroundSelf-citationPremature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
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“Key mediators and inducers of senescence in vitro are p53, p16, and PML (Ferbeyre et al. 2000; Pearson et al. 2000; Narita et al. 2003).”
BackgroundInfluentialSelf-citationInk4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
p53 mutant mice that display early ageing-associated phenotypes
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p53 isoforms can regulate p53 transcriptional activity
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BackgroundBmi1, stem cells, and senescence regulation
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Cited by
Four faces of cellular senescence
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Senescence is a developmental mechanism that contributes to embryonic growth and patterning
Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.041 · Cited by 1,186
Self-citationFat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094
Senescence and aging: the critical roles of p53
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T-helper-1-cell cytokines drive cancer into senescence
Braumüller, H., Wieder, T., Brenner, E., Aßmann, S., Hahn, M., Alkhaled, M., Schilbach, K., Essmann, F., Kneilling, M., Griessinger, C., et al. (2013) · Nature · doi:10.1038/nature11824 · Cited by 720
Metadata
- Authors
- Keyes, W. M., Wu, Y., Vogel, H., Guo, X., Lowe, S. W., & Mills, A. A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-08-17
- Volume
- 19
- Issue
- 17
- Pages
- 1986-1999
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2132408182
- Cited by
- 298
- References
- 12
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Keyes, W. M., Wu, Y., Vogel, H., Guo, X., Lowe, S. W., & Mills, A. A. (2005). p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes & Development. https://doi.org/10.1101/gad.342305
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
