Figure 1. The cellular and molecular pathways relating to aging and age-dependent diseases. At the molecular level, persistent DNA damage response (DDR) leads to activation of the tumor suppressor p53, which in turn activates p21 to initiate cell cycle arrest and induce the senescent cells and apoptosis. The generation of ROS results in mitochondria dysfunction inducing by excessive mutations of mDNA. The internal and external stress triggers the formation of misfolded proteins, and their accumulation contributes to ER malfunction. Respiration declines as a result of mitochondria dysfunction and Insulin resistance because of ER malfunction lead to metabolism alternation. The disrupted process involves Sirt1, and AMPK inhibition that adversely affecting lipid metabolism. Another pathway mediates SASP production that invokes pro-inflammatory pathways resulting in a severe inflammatory response. Excessive immune system activity and metabolic dysfunction at the tissue level are considered as critical age-related diseases promotors (Nah, Yuan, & Jung). ETC (Electron transport chain); ROS (Reactive oxygen species); UPRer (ER unfolded protein response); UPRmt (mitochondrial unfolded protein response); AP-1 (activator protein-1); SASP (senescence-associated secretory phenotype ); NDs (neurodegenerative  diseases); CVDs (Cardiovascular diseases).
Figure 2 The cytokines and chemokines-mediated inflammatory cascades triggered by upregulation and downregulation of pro-inflammatory cytokines and anti-inflammatory factors in age-related diseases.