Hasty Paul, Campisi Judith, Sharp Z Dave
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, Texas 78245, USA.
Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, Texas 78245, USA.
Transl Cancer Res. 2016 Dec;5(6):685-691. doi: 10.21037/tcr.2016.12.02.
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.
p53是一种转录调节因子，可响应细胞应激以抑制肿瘤发生，但其中一些反应可能会产生意想不到的后果，影响与癌症无关的衰老过程。这些后果的影响尚未得到充分理解，部分原因是影响p53功能的过程众多且复杂，部分原因是p53影响的过程范围广泛。p53有可能加速和阻碍细胞衰老过程，这在机体衰老方面可能会产生相反的生物学结果。为了加速衰老，p53诱导细胞凋亡或细胞周期停滞，作为细胞衰老的先决条件；两者都会损害干细胞和祖细胞群体的动员。为了抑制衰老，p53抑制可能导致细胞衰老和衰老相关分泌表型（SASP）的不受调控的增殖途径，而SASP会产生促炎和退化的组织环境。对小鼠模型的综述支持了这两种可能性，突出了p53对机体衰老影响的复杂性。更深入地了解p53如何与各种生物学过程相互整合，将有助于我们更好地理解其对衰老过程的影响。
