Senescence-associated secretory phenotype and its complex regulation networks: A review of molecular mechanisms / 第二军医大学学报

ABSTRACT

Cellular senescence is a state of permanent growth arrest characterized by an irreversible exit from the cell cycle and the secretion of senescence-associated secretory phenotype (SASP). The secretory process of SASP can be roughly divided into three steps: DNA damage response (DDR)-rapid paracrine, early and mature stages. The complex molecular regulation mechanisms of SASP involve DDR, p38 mitogen-activated protein kinase (MAPK) signal pathway, activation of nuclear factor κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), epigenetic alterations of SASP gene, posttranscriptional regulation of gene and autophagy. SASP regulates a variety of pathological states caused by microenvironment changes and has been a drug target to regulate the aging effect, which providing a new therapeutic method for tumor and agerelated pathological states. In this paper, we classified the different types of SASP, reviewed the role of SASP in biological processes and discussed the related molecular mechanisms.