Delayed ageing through damage protection by the Arf/p53 pathway
Abstract
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.
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Mice in which both p53 and p19Arf are overexpressed show delayed ageing.
“mice in which both p53 and p19Arf are overexpressed show delayed ageing 32”
From The common biology of cancer and ageing (2007) · cites this paper as [32]
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- Authors
- Matheu, A., Maraver, A., Klatt, P., Flores, I., Garcia-Cao, I., Borras, C., Flores, J. M., Viña, J., Blasco, M. A., & Serrano, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Serrano, Manuel
- Venue
- Nature
- Published
- 2007-07
- Volume
- 448
- Issue
- 7151
- Pages
- 375-379
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1988008469
- Semantic Scholar
- 37a3bdfa93d3f09de784a1f376300624e93ff8d6
- Cited by
- 466
- References
- 38
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 15 · 2021: 20 · 2020: 14 · 2019: 19 · 2018: 16 · 2017: 21 · 2016: 25 · 2015: 21 · 2014: 21 · 2013: 39 · 2012: 40
- FWCI
- 14.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- ARF-p53 pathway, cellular aging, lifespan extension, tumor resistance, tumor suppression, CDKN2A, antioxidant activity, longevity
- MeSH terms
- Aging, Animals, Antioxidants, Cells, Cultured, Disease Susceptibility, Fibroblasts, Longevity, Neoplasms, Time Factors, Tumor Suppressor Protein p53, Oxidative Stress, Cyclin-Dependent Kinase Inhibitor p16, Mice
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