New insights in cellular senescence: The pituitary model

Pituitary tumors are characterized by slow proliferation rates and a high prevalence within the population. The pathogenesis of these tumors remains incompletely understood, although accumulating evidence suggests that the activation of the cellular senescence program, triggered by various stressors and functioning as a brake on cellular proliferation, may contribute to their typically benign nature. Multiple mediators of the senescence response are implicated in this process. Interleukin-6 (IL-6), a proinflammatory cytokine, plays a dual role in pituitary tumor biology. It is involved in both physiological pituitary growth and the senescence-associated secretory phenotype (SASP), where it mediates paracrine-proliferative signals. In addition to its secretory functions, IL-6 has been implicated in the regulation of pituitary senescence through non-secretory mechanisms. Other factors, such as growth hormone (GH), the pituitary tumor-transforming gene (PTTG), and interactions within the tumor microenvironment, including immune cell dynamics, also contribute to the senescence observed in these tumors. This review examines the latest evidence concerning the role of senescence in pituitary tumors, with a particular focus on the contribution of IL-6 to this process.