Work

Identifying and validating the key regulatory transcription factor YY1 in the aging process of pancreatic beta cells based on bioinformatics

Year: 2024

Type: article

Abstract: The aging of pancreatic beta cells is closely associated with various diseases, such as impaired glucose tolerance, yet the underlying regulatory mechanisms remain unclear. In this study, we screened young and aged mouse pancreatic beta cells' high-throughput sequencing data from the GEO public database. Utilizing bioinformatics techniques, we identified the key regulatory factor YY1 in the aging process of pancreatic islets. We observed a significant decrease in the expression of YY1 in a D-gal-induced mouse model of pancreatic aging and an H 2 O 2 -induced MIN6 cell model of aging. Moreover, both vivo and vitro models, we found that the YY1 agonist eudesmin (EDN) improved glucose intolerance in mice, alleviated aging of pancreatic beta cells, and downregulated the expression of cell cycle protein P21. Mechanistically, we discovered that EDN inhibited the P38/JNK MAPK pathway in aging cells. In summary, our study confirms the regulatory role of the transcription factor YY1 in the aging process of pancreatic beta cells. This finding may provide a new approach for the clinical treatment of pancreatic aging-related diseases such as impaired glucose tolerance or diabetes. • Bioinformatics calculations suggest that the transcription factor YY1 plays a key regulatory role in pancreatic β-cell senescence. • YY1 is downregulated in aging islets and MIN6 cells, and Eudesmin ameliorates this change. • YY1 may improve aging by reducing the phosphorylation levels of P38/JNK MAPK in MIN6 cells. • This study provides new insights or methods for the clinical prevention and treatment of pancreatic aging-related diseases.

Source: Experimental Gerontology

DOI: 10.1016/j.exger.2024.112633