Dioscin integrates regulation of monosaturated fatty acid metabolism to extend the life span through XBP-1/SBP-1 dependent manner
Yi Xiao,
Fang Liu,
Xinting Zhu,
Sanhua Li,
Lingjie Meng,
Nian Jiang,
Changyan Yu,
Haijuan Wang,
Ying Qin,
Jing Hui,
Chunbo Yu,
Yun Liu
Affiliations
Yi Xiao
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; Corresponding author
Fang Liu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China
Xinting Zhu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China
Sanhua Li
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
Lingjie Meng
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
Nian Jiang
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
Changyan Yu
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
Haijuan Wang
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China
Ying Qin
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
Jing Hui
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
Chunbo Yu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China
Yun Liu
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; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China; Corresponding author
Summary: 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 Caenorhabditis elegans. Through the genetic screening in C. elegans, we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPRER 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.
