Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Int J Mol Sci. 2023 Sep 5;24(18):13682. doi: 10.3390/ijms241813682.
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.
动物研究已经证明，1-乙酰基-5-苯基-1H-吡咯-3-基乙酸酯（APPA）是一种新型醛糖还原酶抑制剂，是我们实验室独立合成的，具有强大的抗氧化作用；然而，目前尚无关于 APPA 抗衰老机制的信息。因此，本研究使用该模型研究了 APPA 的抗衰老和抗氧化能力的影响和机制。结果表明，APPA 增加了“寿命”，而不影响 OP50（OP50）的典型代谢。APPA 对 也没有毒性作用，增加了运动能力，降低了活性氧、脂褐素和脂肪的水平，并提高了抗应激能力。实时荧光定量 PCR 分析进一步表明，APPA 上调了抗氧化基因的表达，包括 、 、 和 ，以及胰岛素/胰岛素样生长因子（IGF）受体的关键下游转录因子 、 、 和 。此外， 和 也上调了。然而，APPA 的延长寿命作用在 、 、 和 突变体上不存在，这表明 APPA 的延长寿命机制依赖于胰岛素/IGF-1 信号系统。转录组测序还表明，线粒体途径也与 APPA 的寿命延长密切相关，与 和 突变体的寿命测定结果一致。这些发现有助于研究 APPA 的长寿延长机制。
