The protective effect of cycloastragenol on aging mouse circadian rhythmic disorder induced by d-galactose
The protective effect of cycloastragenol on aging mouse circadian rhythmic disorder induced by d-galactose
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环黄芪醇对D-半乳糖所致衰老小鼠昼夜节律紊乱的保护作用
DOI：
10.1002/jcb.28587
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发表时间：
2019-07-16
影响因子：
4
通讯作者：
Luo, Ying
中科院分区：
文献类型：
--
作者：
Liu, Jing;Gao, Dongxiao;Luo, Ying
哺乳动物的衰老过程与昼夜节律行为的幅度下降和长时间的昼夜节律行为有关，这些昼夜节律行为受视交叉上核（SCN）中的中枢昼夜节律调节器和外周组织中的局部振荡器的调节。目前尚不清楚增强生物钟功能是否能延缓衰老。使用表达per 2：：lucSV的成纤维细胞和衰老细胞，我们揭示了环甘草醇（CAG），一种天然的苷元衍生物从甘草苷IV，作为一个时钟振幅增强小分子。CAG可激活端粒酶抗衰老，但对衰老小鼠昼夜节律紊乱的影响未见报道。在这里，我们分析了CAG对d-半乳糖诱导的衰老小鼠的昼夜节律行为和时钟基因表达的潜在影响。为此目的，每天向d-半乳糖（150 mg/kg，皮下）衰老小鼠模型给予CAG（20 mg/kg口服），持续6周。这些小鼠的自由奔跑活动的actogram分析表明，CAG显着增强自发活动。我们进一步发现CAG增加了衰老小鼠肝脏和肾脏中per 2和bmal 1基因的表达。此外，CAG增强衰老小鼠肝脏和SCN中的时钟蛋白BMAL 1和PER 2水平。结果表明，CAG能恢复d-半乳糖所致衰老小鼠的昼夜节律行为。这些数据表明，CAG可以作为一种新的治疗策略，用于治疗与年龄相关的昼夜节律紊乱。
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.