A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models

作者：Zhao, Yuhan; Wu, Lihua; Yue, Xuetian; Zhang, Cen; Wang, Jianming; Li, Jun; Sun, Xiaohui; Zhu, Yiming; Feng, Zhaohui; Hu, Wenwei^*

来源：eLife, 2018, 7: e34701.

DOI：10.7554/eLife.34701

• HEMATOPOIETIC STEM-CELLS
• CODON 72 POLYMORPHISM
• MICE
• CANCER
• APOPTOSIS
• HUMANS
• DIFFERENTIATION
• DYSFUNCTION
• PHENOTYPES
• PATHOLOGY

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.

• 出版日期2018-3-20
• 单位浙江大学