Knockdown of phosphatases of regenerating liver‐1 prolongs the lifespan of Caenorhabditis elegans via activating DAF‐16/FOXO. Issue 4 (11th March 2023)

• Record Type: Journal Article
• Authors: Yu, Yaoru; Chen, Jing; An, Lu; Huang, Tianci; Wang, Wenbo; Cheng, Ziqi; Wang, Lu; Xu, Xuesong; Zhao, Zhizhuang; Fu, Xueqi; Ma, Junfeng
• Is Part Of: FASEB journal. Volume 37:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-11
• Subjects: phosphatases of regenerating liver -- PRL -- Caenorhabditis elegans -- lifespan -- DAF‐16 -- ROS; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202202003R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Phosphatases of regenerating liver (PRLs) are dual‐specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans ( C. elegans ). Structurally, this phosphatase in C. elegans, named PRL‐1, consisted of a conserved signature sequence WPD loop and a single C(X)5 R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL‐1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding‐based RNA‐interference method, knockdown of prl‐1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl‐1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin‐like growth factor 1 signaling pathway, and SIR‐2.1 but through a DAF‐16‐dependent pathway. Moreover, knockdown of prl‐1 induced the nuclear translocation of DAF‐16, and upregulated the expression of daf‐16, sod‐3, mtl‐1, and ctl‐2 . Finally, suppression of prl‐1 also reduced the ROS. In conclusion, suppression of prl‐1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases. Abstract : We reported for the first time that knockdown of prl‐1 could not only prolong the lifespan but also improve the health of Caenorhabditis elegans . Besides, the lifespan‐regulating effect of prl‐1 in C. elegans appeared to be through a DAF‐16‐dependent pathway. The prl‐1 could induce the nuclear translocation of DAF‐16 and upregulate the expression of daf‐16, sod‐3, mtl‐1, and ctl‐2 genes. Finally, ROS levels were also proved to be reduced by the suppression of prl‐1, which could be a potential mechanism of the lifespan extension mediated by PRL‐1 in C. elegans .