Suppressed cellular senescence mediated by T-box3 in aged gastric epithelial cells may contribute to aging-related carcinogenesis

Aging is a risk factor of carcinogenesis in various organs, and abnormal aging of the stem cells is considered responsible for carcinogenesis. Recent advances in organoid culturing system have made it viable to investigate mini organs developed from tissue stem cells. In this study, we aimed to investigate the implications of aging stem cells for gastric carcinogenesis. We found that gastric organoids of aged mice grew larger in size and proliferated vigorously compared to that of young mice. To elucidate the mechanism involved in this difference, we extracted the total RNA from the organoids and subjected it to microarray analysis, which revealed that the expression of transcription factor T-box 3 (Tbx3) was enhanced in aged gastric organoids. Further studies showed that this enhanced Tbx3 expression suppressed cellular senescence and enhanced proliferation. We utilized microarray analysis to find out the gene responsible for restraining cellular senescence in aged gastric organoids. Gastric organoids were established from young and aged murine stomachs. Total RNA was extracted from the organoids and was subjected to microarray analysis.