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doi: 10.1002/jcp.27306 272

Hyperactivation of oncogenes leads to excessive replication stress and activation of the DDR pathway.15 Oxidative Stress and Mitochondrial Dysfunction: Reactive oxygen species (ROS) generated from mitochondrial dysfunction or environmental stress contribute to cellular senescence.16 Oxidative stress leads to DNA damage, lipid peroxidation, and protein dysfunction.17 ROS can activate the p38 MAPK pathway, which enhances p53 and p16 signaling, reinforcing senescence.18 Importantly, oxidative stress is not an isolated mechanism but a central upstream driver of the SASP