Xiao Yi, Liu Fang, Zhu Xinting, Li Sanhua, Meng Lingjie, Jiang Nian, Yu Changyan, Wang Haijuan, Qin Ying, Hui Jing, Yu Chunbo, Liu Yun
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China.
Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China.
iScience. 2023 Feb 24;26(3):106265. doi: 10.1016/j.isci.2023.106265. eCollection 2023 Mar 17.
Delay aging, especially in healthy life extension, brought the most interest to the medical field. Searching for anti-aging drugs with relative safety profiles bring natural products in hotspot. In this study, we find that dioscin promotes the health span extension in wild-type . Through the genetic screening in , we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPR transcription factor XBP-1 to upregulate transcription of the Δ9 desaturase FAT-5 and FAT-7, resulting in increased monounsaturated fatty acid content which requires for healthy life span extension. Intriguingly, through tissue-specific knockdown, we find that dioscin modulates the health span by activating SBP-1 in the intestine. Unexpectedly, dietary supplementation of POA and OA rescues XBP-1, SBP-1 mutants-induced shortened life span phenotype. Considering the conservation of MUFAs metabolism, dioscin may promote health span in other species, including mammals. Our work suggests that dioscin might be a promising candidate for developing anti-aging agent.
延缓衰老，尤其是在健康寿命延长方面，引起了医学领域的极大兴趣。寻找具有相对安全特性的抗衰老药物使得天然产物成为热点。在本研究中，我们发现薯蓣皂苷促进野生型生物的健康寿命延长。通过在……中的基因筛选，我们进一步揭示薯蓣皂苷通过未折叠蛋白反应转录因子XBP-1激活转录因子SBP-1/SREBP，从而上调Δ9去饱和酶FAT-5和FAT-7的转录，导致单不饱和脂肪酸含量增加，而这是健康寿命延长所必需的。有趣的是，通过组织特异性敲低，我们发现薯蓣皂苷通过激活肠道中的SBP-1来调节健康寿命。出乎意料的是，膳食补充POA和OA可挽救XBP-1、SBP-1突变体诱导的寿命缩短表型。考虑到单不饱和脂肪酸代谢的保守性，薯蓣皂苷可能在包括哺乳动物在内的其他物种中促进健康寿命。我们的工作表明薯蓣皂苷可能是开发抗衰老药物的一个有前途的候选物。
