Relevance of the p53–MDM2 axis to aging
Open accessAbstract
In response to varying stress signals, the p53 tumor suppressor is able to promote repair, survival, or elimination of damaged cells - processes that have great relevance to organismal aging. Although the link between p53 and cancer is well established, the contribution of p53 to the aging process is less clear. Delineating how p53 regulates distinct aging hallmarks such as cellular senescence, genomic instability, mitochondrial dysfunction, and altered metabolic pathways will be critical. Mouse models have further revealed the centrality and complexity of the p53 network in aging processes. While naturally aged mice have linked longevity with declining p53 function, some accelerated aging mice present with chronic p53 activation, whose phenotypes can be rescued upon p53 deficiency. Further, direct modulation of the p53-MDM2 axis has correlated elevated p53 activity with either early aging or with delayed-onset aging. We speculate that p53-mediated aging phenotypes in these mice must have (1) stably active p53 due to MDM2 dysregulation or chronic stress or (2) shifted p53 outcomes. Pinpointing which p53 stressors, modifications, and outcomes drive aging processes will provide further insights into our understanding of the human aging process and could have implications for both cancer and aging therapeutics.
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Development of MDM2/MDMX dual-target inhibitors may solve the problems existing in clinical research of MDM2 inhibitors and has great practical significance for treatment of related tumors.
“It seems that the development of MDM2/MDMX dual-target inhibitors may solve the problems existing in the clinical research of the above MDM2 inhibitors and has great practical significance for the treatment of related tumors [97, 108, 109].”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [109]
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Multifaceted role for p53 in pancreatic cancer suppression
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Rubin de Celis, M. F., Garcia-Martin, R., Syed, I., Lee, J., Aguayo-Mazzucato, C., Bonner-Weir, S., & Kahn, B. B. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2206923119 · Cited by 39 · see citing works
- Authors
- Wu, D., & Prives, C.
- Affiliations
- Columbia University (US)
- Corresponding author
- Prives, Carol
- ORCID
- Prives, Carol
- Venue
- Cell Death & Differentiation
- Published
- 2017-12-01
- Volume
- 25
- Issue
- 1
- Pages
- 169-179
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC5729541
- OpenAlex
- W2774396895
- Cited by
- 215
- References
- 41
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 21 · 2023: 33 · 2022: 34 · 2021: 24 · 2020: 39 · 2019: 15 · 2018: 7 · 2017: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA058316, CA 58316)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- p53, MDM2, aging, cellular senescence, genomic instability, mitochondrial dysfunction, metabolic aging, accelerated aging, p53 deficiency, stress response, longevity, cancer therapeutics
- MeSH terms
- Aging, Animals, Humans, Longevity, Neoplasms, Tumor Suppressor Protein p53, Aging, Premature, Mice, Proto-Oncogene Proteins c-mdm2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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