Laboratory of Molecular Genetics of Aging and Tumor, Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China.
J Cell Biochem. 2019 Oct;120(10):16408-16415. doi: 10.1002/jcb.28587. Epub 2019 Jul 16.
Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. It is unclear whether enhancing clock function can retard aging. Using fibroblasts expressing per2::lucSV and senescent cells, we revealed cycloastragenol (CAG), a natural aglycone derivative from astragaloside IV, as a clock amplitude enhancing small molecule. CAG could activate telomerase to antiaging, but no reports focused on its effects on circadian rhythm disorders in aging mice. Here we analyze the potential effects of CAG on d-galactose-induced aging mice on the circadian behavior and expression of clock genes. For this purpose, CAG (20 mg/kg orally), was administered daily to d-galactose (150 mg/kg, subcutaneous) mice model of aging for 6 weeks. An actogram analysis of free-running activity of these mice showed that CAG significantly enhances the locomotor activity. We further found that CAG increase expressions of per2 and bmal1 genes in liver and kidney of aging mouse. Furthermore, CAG enhanced clock protein BMAL1 and PER2 levels in aging mouse liver and SCN. Our results indicated that the CAG could restore the behavior of circadian rhythm in aging mice induced by d-galactose. These data of present study suggested that CAG could be used as a novel therapeutic strategy for the treatment of age-related circadian rhythm disruption.
哺乳动物的衰老过程与节律行为的振幅降低和周期延长有关，这些节律行为受视交叉上核（SCN）中的中央生物钟调节器和外周组织中的局部振荡器调节。目前尚不清楚增强时钟功能是否能延缓衰老。我们使用表达 per2::lucSV 的成纤维细胞和衰老细胞发现，天然黄芪甲苷 IV 的苷元衍生物环黄芪醇（CAG）是一种能增强时钟振幅的小分子。CAG 可以激活端粒酶来抗衰老，但没有报道专门针对其对衰老小鼠昼夜节律紊乱的影响。在这里，我们分析了 CAG 对 D-半乳糖诱导的衰老小鼠昼夜行为和时钟基因表达的潜在影响。为此，我们用 CAG（20mg/kg，口服）每天处理 D-半乳糖（150mg/kg，皮下）诱导的衰老小鼠模型 6 周。这些小鼠的自由活动节律分析表明，CAG 显著增强了运动活性。我们进一步发现 CAG 增加了衰老小鼠肝脏和肾脏中 per2 和 bmal1 基因的表达。此外，CAG 增加了衰老小鼠肝脏和 SCN 中生物钟蛋白 BMAL1 和 PER2 的水平。我们的结果表明，CAG 可以恢复 D-半乳糖诱导的衰老小鼠的昼夜节律行为。本研究的数据表明，CAG 可作为治疗与年龄相关的昼夜节律紊乱的一种新的治疗策略。
