Fig. 3

The formation of SASP in senescent cell. The formation of SASP undergoes multiple mechanism and regulator; many time-dependent damage will accelerate the formation of SASP. Actually, transformation of SASP involves many signaling pathways. The deletion of p53 and the upregulated expression of RAS aggravate the paracrine activity of SASP. Besides, the three-dimensional structure of the genome in senescent cells can enhance the SAE activity through the transcription factor C/EBPα/β, thereby promoting the secretion of SASP. DDR-dependent SASP activation accompanies by chromatin remodeling frequently, in which HDAC might be involved. SAE SASP of senescent cells also damages the DNA of adjacent cells and induces senescence, thereby forming senescence-induced senescence. The cytoplasm alternation is also involved in aging and tumors. ROS is a by-product of mitochondrial electron transfer in aerobic cells. High levels of ROS will lead to cell damage and increase genomic instability to exert oncogenic functions. In the process of aging, dysfunction mitochondria will gradually accumulate, and events including membrane potential reduction and proton leakage will occur, eventually leading to increased ROS levels. Not only that, changes in mitochondria will cause corresponding changes in AMP/ATP, AMP/ATP, and NAD + /NADH ratios, thereby leading to cell cycle arrest, NF-κB activation, and other changes that are considered important to tumor formation. Transcribed by NF-κB and other factors, and translated in an mTOR-dependent manner contributing to the robust secretion of SASP-related inflammatory cytokines, chemokines, angiogenic growth, and ECM-degrading signals. SASP, senescence-associated secretory phenotype; DDR, DNA damage response; SAE, senescence activation enhancer; C/EBPα/β, CCAAT/enhancer-binding protein α/β; HDAC, histone deacetylase; ATP, adenosine triphosphate; AMP, adenosine monophosphate