A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 20, 2018
- Source ID
- 10.7554/elife.34701
Entities
People
- Cen Zhang
- Jianming Wang
- Jun Li
- Lihua Wu
- Wenwei Hu
- Xiaohui Sun
- Xuetian Yue
- Yiming Zhu
- Yuhan Zhao
- Zhaohui Feng
Organizations
- Lawrence Ellison Foundation
- National Institutes of Health
- Rutgers University
- United States Department of Defense
- Zhejiang University