Recently, the quest for the mythical fountain of youth has turned into specific research programs aiming to extend the healthy lifespan of humans. Despite advances in our understanding of the molecular processes underlying aging, the surprisingly extended lifespan of some animals remains unexplained. In this respect, the p53 protein plays a crucial role not only in tumor suppression but also in tissue homeostasis and healthy aging. However, the mechanism through which p53 maintains the function as a gatekeeper of healthy aging is not fully understood. Thus, we inspected TP 53 gene sequences in individual species of phylogenetically related organisms that show different aging patterns. We discovered novel correlations between specific amino acid variations in p53 and lifespan across different animal species. In particular, we found that species with extended lifespan have characteristic amino acid substitutions mainly in the p53 DNA binding domain that change its function. Our findings show a direct association of specific amino acid residues in p53 protein with extended organismal lifespan and the importance of p53 protein in aging. ### Competing Interest Statement The authors have declared no competing interest.