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.

中文翻译：

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肿瘤抑制基因 p53 的多态性影响小鼠模型的衰老和寿命

肿瘤抑制因子 p53 可防止因癌症发展而导致的早期死亡。然而，p53 在衰老过程和长寿中的作用尚未确定。在人类中，密码子 72 处带有精氨酸 (R72) 或脯氨酸 (P72) 的单核苷酸多态性 (SNP) 会影响 p53 的活性；P72 等位基因在肿瘤抑制中具有较弱的 p53 活性和功能。在这里，我们采用敲入携带密码子 72 SNP 的人类 TP53 基因的小鼠模型，我们发现尽管癌症风险增加，但逃避肿瘤发展的 P72 小鼠比 R72 小鼠显示出更长的寿命。此外，与 R72 小鼠相比，P72 小鼠的衰老相关表型发育延迟。从机制上讲，与 R72 小鼠相比，P72 小鼠在衰老过程中可以更好地保留干/祖细胞的自我更新功能。