The vicious cycle of DNA damage-cellular senescence-damage accumulation constitutes a core regulatory network for individual aging and the occurrence and development of age-related diseases. DNA damage can drive the cellular senescence process through three major pathways, thus activating the DNA-damage response (DDR) pathway, inducing telomere dysfunction and initiating senescence-associated secretory phenotype (SASP). Cells that enter the senescent state can further exacerbate DNA damage accumulation through enhanced oxidative stress mediated by SASP factors, as well as the decline in their own DNA damage repair capacity and autophagy dysfunction. This vicious cycle not only directly leads to the progressive decline of the functions of various tissues and organs in the body, but also promotes the pathological progression of various diseases such as tumors and neurodegenerative disorders by promoting the accumulation of genetic mutations, inducing the formation of chronic inflammatory microenvironments and weakening the immune function of the body. This article takes DNA damage as the entry point to explore the mechanism and effect of DNA damage-cell senescence-damage accumulation.

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