Insulin resistance and oxidative stress as the core of the classical mechanism of promoting aging. T2DM is typically characterized by chronic hyperglycemia and IR. Mechanistically, high glucose induces cellular production of ROS (O2-, H2O2, and -HO) leading to mitochondrial dysfunction and DNA damage (telomere shortening), and triggers persistent epigenetic changes, chronic inflammation, protein misfolding, and cellular senescence through NF-κB, p38/MAPK, and TORC1 (mTOR)-mediated pathways. Inflammation, protein misfolding and cellular senescence through NF-κB, p38/MAPK and TORC1 (mTOR)-mediated pathways. Activation of the NF-κB signaling pathway by oxidative stress inhibits the normal tyrosine phosphorylation of the insulin receptor InsR and the insulin receptor substrate IRS. It reduces the gene and protein expression of GLUT4, ultimately leading to IR and hyperinsulinemia. On the one hand, target cells chronically exposed to high insulin concentrations promote the expression of cellular senescence markers through enhanced insulin-like growth factor (IGF) transactivation, which leads to cellular senescence; on the other hand, high insulin concentrations negatively affect the cell division program through downstream PI3K/Akt and mTOR signaling, which leads to cellular senescence. NF-κB: Nuclear factor kappa B; IGF-1R:Insulin-like growth factor 1 receptor; PI3K/Akt: Phosphoinositide 3-Kinase/protein kinase B; mTORC2: Mechanistic target of rapamycin complex 2; SA-β-gal：Senescence-associated β-galactosidase.