Cited by 466Genetics, Aging, and Longevity in Model OrganismsCancer-related Molecular PathwaysTelomeres, Telomerase, and Senescence

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Delayed ageing through damage protection by the Arf/p53 pathway

Matheu, Ander, Maraver, Antonio, Klatt, Peter, Flores, Ignacio, Garcia-Cao, Isabel, Borras, Consuelo, Flores, Juana M., Viña, Jose, Blasco, Maria A., Serrano, Manuel·2007·Nature

DOI 10.1038/nature05949

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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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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
ORCID: Matheu, Ander
Maraver, Antonio
Flores, Ignacio
Flores, Juana M.
Serrano, Manuel
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-07
Volume: 448
Issue: 7151
Pages: 375-379
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature05949
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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Delayed ageing through damage protection by the Arf/p53 pathway

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