| Summary: | 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.
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