PDF(Pubmed)
Abstract：
Compounds with lifespan extension activity are rare, although increasing research efforts have been invested in this field to find ways to extend healthy lifespan. By applying a yeast-based high-throughput assay to identify the chronological lifespan extension activity of mulberry extracts rapidly, we demonstrated that a group of prenylated flavones, particularly morusin and mulberrin, could extend the chronological lifespan of budding yeast via a nutrient-dependent regime by at least partially targeting SCH9. Their antiaging activity could be extended to C. elegans by promoting its longevity, dependent on the full functions of genes akt-1 or akt-2. Moreover, additional benefits were observed from morusin- and mulberrin-treated worms, including increased reproduction without the influence of worm health (pumping rate, pumping decline, and reproduction span). In the human HeLa cell model, morusin and mulberrin inhibited the phosphorylation of p70S6K1, promoted autophagy, and slowed cell senescence. The molecular docking study showed that mulberrin and morusin bind to the same pocket of p70S6K1. Collectively, our findings open up a potential class of prenylated flavones performing their antiaging activity via nutrient-sensing pathways.
摘要：
具有延长寿命活性的化合物很少，尽管在这一领域投入了越来越多的研究努力，以寻找延长健康寿命的方法。通过应用基于酵母的高通量测定法快速鉴定桑树提取物的按时间顺序延长寿命的活性，我们证明了一组异戊二烯化的黄酮，尤其是莫鲁辛和莫伯林,通过至少部分靶向SCH9，可以通过营养依赖性方案延长出芽酵母的时间寿命。它们的抗衰老活性可以通过促进秀丽隐杆线虫的寿命来扩展，依赖于基因akt-1或akt-2的全部功能。此外，从莫鲁辛和莫伯林治疗的蠕虫中观察到额外的好处，包括在不受蠕虫健康影响的情况下增加繁殖(抽水率，抽水下降，和繁殖跨度)。在人类HeLa细胞模型中,morusin和mulberrin抑制p70S6K1的磷酸化，促进自噬，减缓细胞衰老。分子对接研究表明，莫伯林和莫鲁素与p70S6K1的同一个口袋结合。总的来说，我们的发现开辟了一类潜在的异戊烯化黄酮,它们通过营养感知途径发挥抗衰老作用.
