Do p53 stress responses impact organismal aging?
p53 is a transcriptional regulator that responds to cellular stresses to suppress oncogenesis, but some of these responses can have unintended consequences that influence non-cancer-related aging processes. The impact of these consequences is not well understood—partly due to the many complex processes that influence p53 function and partly due to the vast array of processes that p53 affects. p53 has the potential to both accelerate and hinder cellular aging processes, which would likely have antithetical biological outcomes with regard to organismal aging. To accelerate aging, p53 induces apoptosis or cell cycle arrest as a prerequisite to cellular senescence; both can impair the mobilization of stem and progenitor cell populations. To suppress aging, p53 inhibits unregulated proliferation pathways that could lead to cellular senescence and a senescence-associated secretory phenotype (SASP), which creates a pro-inflammatory and degenerative tissue milieu. A review of mouse models supports both possibilities, highlighting the complexity of the p53 influence over organismal aging. A deeper knowledge of how p53 integrates and is integrated with various biological processes will improve our understanding of its influence over the aging process.