Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury

Acute kidney injury (AKI), a life-threatening disorder marked by abrupt renal dysfunction, is increasingly recognized as a global healthcare challenge. It not only triggers immediate organ dysfunction but also heightens long-term risks of chronic kidney disease (CKD). The senescence of proximal tubular epithelial cells (PTECs) has a major impact on the occurrence and development of AKI. This review systematically analyzes existing evidence, which suggests that the senescence of PTECs may have a dual effect. Acute cellular senescence typically mitigates uncontrolled replication of damaged cells by inducing cell cycle arrest, thereby limiting the further expansion of tissue damage. In contrast, the pathological retention of chronic senescent cells and the excessive production of the senescence-associated secretory phenotype (SASP) exacerbate the local inflammatory response and the process of fibrosis, accelerating the transformation of AKI into CKD. Despite incomplete elucidation of the spatiotemporal mechanisms governing the transition from acute to chronic cellular senescence, therapeutic interventions can be precisely targeted to specific disease stages based on their characteristic progression dynamics. This review summarizes the intervention strategies applicable at different stages of AKI, including prevention, early induction of senescence, senoreverse, senolysis, and senomorphics. Additionally, we highlight potential therapeutic targets to provide a theoretical basis for optimizing clinical management.