A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models
- Rutgers, The State University of New Jersey, United States
- Zhejiang University, China
Abstract
Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice. Further, P72 mice have a delayed development of aging-associated phenotypes compared with R72 mice. Mechanistically, P72 mice can better retain the self-renewal function of stem/progenitor cells compared with R72 mice during aging. This study provides direct genetic evidence demonstrating that p53 codon 72 SNP directly impacts aging and longevity, which supports a role of p53 in regulation of longevity.
Article and author information
Author details
Funding
Lawrence Ellison Foundation (New Investigate Award AG-NS-0781-11)
- Wenwei Hu
National Institutes of Health (1R01CA160558)
- Wenwei Hu
National Institutes of Health (1R01CA203965)
- Wenwei Hu
National Institutes of Health (F99CA222734)
- Yuhan Zhao
National Institutes of Health (1R01CA227912)
- Zhaohui Feng
- Wenwei Hu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Maureen Murphy, The Wistar Institute, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animal experiments were approved by institutional animal care and use committee (IACUC) protocol (I14-012) of the University of Rutgers.
Version history
- Received: December 28, 2017
- Accepted: March 18, 2018
- Accepted Manuscript published: March 20, 2018 (version 1)
- Version of Record published: April 18, 2018 (version 2)
Copyright
© 2018, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models
eLife 7:e34701.
https://doi.org/10.7554/eLife.34701
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