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

doi:10.1016/j.isci.2023.106265

Dioscin integrates regulation of monosaturated fatty acid metabolism to extend the life span through XBP-1/SBP-1 dependent manner

iScience. 2023 Feb 24;26(3):106265. doi: 10.1016/j.isci.2023.106265. eCollection 2023 Mar 17.

Authors

Yi Xiao^{1

2}, Fang Liu^{1

3}, Xinting Zhu^{1

3}, Sanhua Li^{1

2}, Lingjie Meng^{1

2}, Nian Jiang^{1

2}, Changyan Yu^{1

2}, Haijuan Wang¹, Ying Qin^{1

2}, Jing Hui^{1

2}, Chunbo Yu^{1

3}, Yun Liu^{1

2

3}

Affiliations

¹ Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China.
² Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China.
³ College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China.

Abstract

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 UPR^ER 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.

Keywords: Biochemistry; Biological sciences; Physiology.