Mdm2–p53 signaling regulates epidermal stem cell senescence and premature aging phenotypes in mouse skin
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The p53 transcription factor is activated by various types of cell stress or DNA damage and induces the expression of genes that control cell growth and inhibit tumor formation. Analysis of mice that express mutant forms of p53 suggest that inappropriate p53 activation can alter tissue homeostasis and life span, connecting p53 tumor suppressor functions with accelerated aging. However, other mouse models that display increased levels of wildtype p53 in various tissues fail to corroborate a link between p53 and aging phenotypes, possibly due to the retention of signaling pathways that negatively regulate p53 activity in these models. In this present study, we have generated mice lacking Mdm2 in the epidermis. Deletion of Mdm2, the chief negative regulator of p53, induced an aging phenotype in the skin of mice, including thinning of the epidermis, reduced wound healing, and a progressive loss of fur. These phenotypes arise due to an induction of p53-mediated senescence in epidermal stem cells and a gradual loss of epidermal stem cell function. These results reveal that activation of endogenous p53 by ablation of Mdm2 can induce accelerated aging phenotypes in mice.
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Skin of the mouse lacking the negative regulatory protein of p53, MDM2, elicited increased basal p53 level and premature aging skin phenotypes, including thinning of the epidermis, reduced wound healing, and progressive hair loss.
“Skin of the mouse lacking the negative regulatory protein of p53, MDM2, elicited increased basal p53 level and premature aging skin phenotypes, including thinning of the epidermis, reduced wound healing, and progressive hair loss [68].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [68]
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- Authors
- Gannon, H. S., Donehower, L. A., Lyle, S., & Jones, S. N.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Baylor College of Medicine (US)
- Corresponding author
- Jones, Stephen N.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 353
- Issue
- 1
- Pages
- 1-9
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC3075331
- OpenAlex
- W1996846864
- Cited by
- 87
- References
- 44
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 8 · 2015: 3 · 2014: 8 · 2013: 8 · 2012: 8
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- NIDDK (DK32520)
- National Cancer Institute (CA077735)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- MDM2, p53, epidermal stem cells, cellular senescence, premature aging, skin aging, epidermal thinning, wound healing, p53 tumor suppressor, tissue homeostasis
- MeSH terms
- Epidermal Cells, Animals, Phenotype, Stem Cells, Signal Transduction, Skin Aging, Tumor Suppressor Protein p53, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Mice, Proto-Oncogene Proteins c-mdm2
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