The relationship between CXC chemokines and cellular senescence: from mechanisms to therapy

Chemokines are small molecule secreted proteins that regulate biological processes such as chemotaxis, hematopoiesis, and angiogenesis, typically functioning through binding to G-protein-coupled receptors (GPCRs) on the cell surface. The chemokine family can be classified into four major types based on the differences in their conserved cysteine motifs at the N-terminal: CC, CXC, CX3C, and XC. Among them, the CXC family occupies a central position in the chemokine group. Due to their vital role in biological processes, chemokines have become a key focus of research in various complex diseases. Cell senescence is linked to various factors, including DNA damage and telomere shortening, marked by cell cycle arrest. Senescent cells impact both local and systemic microenvironments via the senescence-associated secretory phenotype (SASP), and CXC chemokines, as critical components of SASP, have been demonstrated to play important roles in various age-related diseases and cancers. However, the role of chemokines, especially CXC chemokines, in cellular senescence and the diseases they mediate has not been fully elucidated. This review summarizes the mechanism of action of CXC chemokines, the latest progress in their role in cellular senescence and related diseases, and discusses the potential of CXC chemokines as biomarkers and therapeutic targets.