Radiation-induced cellular senescence in salivary glands

Abstract

Aging is the process of becoming older. Biologically, aging refers to cells within an organ which have stopped dividing and can produce unfavorable factors, the so-called senescent cells. These cells may induce deterioration of neighboring cells and consequential organ dysfunction. Several studies have shown that senescent cells might be involved in the progression of many diseases, like pulmonary fibrosis, cancer, neurodegenerative diseases and atherosclerosis, making senescent cells an attractive therapeutic target. Loss of saliva production and consequential dry mouth syndrome (xerostomia) is a severe side effect of radiotherapy for head and neck cancer due to the co-irradiation of the salivary glands. It has been shown that radiation-induced cellular senescence (or early aging) may play an important role in this loss of salivary gland function. The main goal of this thesis is to characterize and modulate radiation-induced senescence in the salivary gland in relation to tissue regeneration potential. We identified that irradiation can induce cellular senescence both in a laboratory organoid model as well as in tissue. Next to this, a novel radiation-induced senescence marker called Glial Cell Derived Neurotrophic Factor (GDNF) was identified. Interestingly it was shown that the selective elimination of premature aged senescent cells can improve the saliva production after radiation. Our research may open a potential new avenue for the treatment of radiation-induced xerostomia and provide a better environment for stem cell transplantation therapy. This could have important future implications for improving the quality of life of head and neck cancer patients.