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

Area of Science:

• Genetics
• Aging Research
• Molecular Biology

Background:

• The tumor suppressor protein p53 is crucial for preventing cancer.
• Its specific role in the aging process and longevity remains unclear.
• A common human single nucleotide polymorphism (SNP) in the TP53 gene at codon 72 results in either arginine (R72) or proline (P72) variants, affecting p53 activity.

Purpose of the Study:

• To investigate the impact of the p53 codon 72 SNP on aging and longevity.
• To determine if different p53 variants influence age-related phenotypes and stem cell function.

Main Methods:

• Utilized a mouse model engineered with a knock-in of the human TP53 gene harboring the codon 72 SNP.
• Compared lifespan, aging-associated phenotypes, and stem/progenitor cell self-renewal capacity between mice with R72 and P72 alleles.

Main Results:

• Mice with the P72 allele (weaker p53 activity) exhibited a longer lifespan than R72 mice, despite an increased risk of cancer.
• P72 mice demonstrated delayed onset of aging-associated phenotypes compared to R72 mice.
• Mechanistically, P72 mice better maintained stem/progenitor cell self-renewal during aging.

Conclusions:

• The p53 codon 72 SNP directly influences aging and longevity.
• p53 plays a regulatory role in longevity, with specific variants impacting lifespan and aging.
• Genetic variations in p53 can modulate aging trajectories independently of tumor suppression.