Inflammatory Amplification Network Driven by Senescent Cells and Strategies for Homeostatic Restoration

Cellular senescence is an essential biological program that protects tissues from diverse forms of stress and damage. However, with aging, senescent cells accumulate abnormally and continuously secrete the senescence-associated secretory phenotype (SASP), thereby driving inflammaging and promoting the development of multiple age-related diseases. Emerging evidence indicates that senescent cells mediate chronic inflammation through SASP and further induce immunosenescence and gut microbiota dysbiosis. These three processes interact to establish a self-amplifying inflammatory network, accelerating functional decline during aging. This review summarizes the interplay among cellular senescence, immunosenescence, and gut microbiota dysbiosis, as well as their underlying mechanisms in the development of inflammaging. In addition, current therapeutic strategies, including senescent cell clearance, restoration of immune homeostasis, and modulation of the gut microbiota, are discussed, providing new insights into delaying aging and preventing age-related diseases.