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

eLife | Mar 20, 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 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.

Pubmed ID: 29557783 RIS Download

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Associated grants

  • Agency: U.S. Department of Defense, Id: W81XWH-16-1-0358
  • Agency: NCI NIH HHS, Id: R01 CA203965
  • Agency: New Jersey Commission on Cancer Research, Id: Postdoctoral Fellowship Award
  • Agency: NCI NIH HHS, Id: R01 CA160558
  • Agency: NCI NIH HHS, Id: P30 CA072720
  • Agency: NCI NIH HHS, Id: R01 CA227912
  • Agency: National Institutes of Health, Id: 1R01CA160558
  • Agency: National Institutes of Health, Id: F99CA222734
  • Agency: National Institutes of Health, Id: 1R01CA203965
  • Agency: Lawrence Ellison Foundation, Id: New Investigate Award AG-NS-0781-11
  • Agency: NCI NIH HHS, Id: F99 CA222734
  • Agency: National Institutes of Health, Id: 1R01CA227912

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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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