APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway in .

Animal studies have proven that 1-acetyl-5-phenyl-1H-pyrrol-3-yl acetate (APPA) is a powerful antioxidant as a novel aldose reductase inhibitor independently synthesized by our laboratory; however, there is no current information on APPA's anti-aging mechanism. Therefore, this study examined the impact and mechanism of APPA's anti-aging and anti-oxidation capacity using the model. The results demonstrated that APPA increases ' longevity without affecting the typical metabolism of OP50 (OP50). APPA also had a non-toxic effect on , increased locomotor ability, decreased the levels of reactive oxygen species, lipofuscin, and fat, and increased anti-stress capacity. QRT-PCR analysis further revealed that APPA upregulated the expression of antioxidant genes, including , , and , and the critical downstream transcription factors, , , and of the insulin/insulin-like growth factor (IGF) receptor, . In addition, and were upregulated. However, the APPA's life-prolonging effects were absent on the , , , and mutants implying that the APPA's life-prolonging mechanism depends on the insulin/IGF-1 signaling system. The transcriptome sequencing also revealed that the mitochondrial route was also strongly associated with the APPA life extension, consistent with and mutant life assays. These findings aid in the investigation of APPA's longevity extension mechanism.