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Significance The incidence of type 1 and type 2 diabetes is increasing worldwide. Senescence in pancreatic beta cells is a major contributor to diabetes development. New treatments for cellular senescence… Click to show full abstract
Significance The incidence of type 1 and type 2 diabetes is increasing worldwide. Senescence in pancreatic beta cells is a major contributor to diabetes development. New treatments for cellular senescence are needed to prevent diabetes and its comorbidities. Available senolytics kill senescent cells and reduce cell mass. Here, we discovered that the endogenous lipids palmitic acid hydroxy stearic acids (PAHSAs) prevent and reverse beta cell senescence in autoimmune diabetic mice, clonal beta cells, and human pancreatic islets exposed to metabolic stressors. PAHSAs act by inducing expression of negative regulators of p53 such as Mdm2 and by enhancing protective pathways such as glutathione metabolism and DNA repair. Therefore, PAHSAs have the therapeutic potential to modulate senescence to prevent and reverse diabetes.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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