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

eLife | 2018

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 humangene 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.

Pubmed ID: 29557783 RIS Download

Mesh terms: Aging | Alleles | Amino Acid Substitution | Animals | Codon | Humans | Longevity | Mice, 129 Strain | Mice, Inbred C57BL | Mice, Transgenic | Models, Animal | Mutation, Missense | Polymorphism, Single Nucleotide | Transgenes | Tumor Suppressor Protein p53

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA203965
  • Agency: NCI NIH HHS, United States
    Id: R01 CA160558
  • Agency: NCI NIH HHS, United States
    Id: P30 CA072720
  • Agency: NCI NIH HHS, United States
    Id: R01 CA227912
  • Agency: NIH HHS, United States
    Id: 1R01CA160558
  • Agency: NIH HHS, United States
    Id: F99CA222734
  • Agency: NIH HHS, United States
    Id: 1R01CA203965
  • Agency: NCI NIH HHS, United States
    Id: F99 CA222734
  • Agency: NIH HHS, United States
    Id: 1R01CA227912

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