阿魏酸通过胰岛素/IGF信号通路和DAF-16促进秀丽隐杆线虫寿命和应激抵抗力  

Ferulic Acid Promotes Longevity and Stress Tolerance via the Insulin/IGF Signaling Path⁃way and DAF-16 in Caenorhabditis Elegans

作　　者：况琪斐 陈巧超 张玲[1] 何文[1] 裴中[2] KUANG Qi-fei;CHEN Qiao-chao;ZHANG Ling;HE Wen;PEI Zhong(Department of Geriatrics,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Depart-ment of Neurology,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院老年医学科,广东广州510080 [2]中山大学附属第一医院神经内科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2021年第2期193-201,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然基金(81671102);广州市科技计划项目(202002020011)。

摘　　要：【目的】观察阿魏酸对秀丽隐杆线虫寿命及应激抵抗能力的影响,探究其可能机制。【方法】使用秀丽隐杆线虫作为抗衰老模型,给予不同浓度的阿魏酸(0、1、10、50 mmol/L),探究其对线虫寿命、抗应激能力、脂褐素水平的调控作用;使用qPCR筛选衰老相关基因,采用daf-2(DR1572)、daf-16(CF1038)突变体线虫,对阿魏酸的潜在作用机理进行初步探讨。【结果】与空白对照组相比,阿魏酸能明显延长秀丽隐杆线虫寿命并提高抗氧化应激和热应激能力(P<0.001),抑制与衰老相关的脂褐素的沉积(P<0.001),同时不影响生育力和发育(P>0.05)。用50 mmol/L阿魏酸组喂养线虫后,daf-2、akt-2和age-1基因的mRNA表达水平下调(P<0.05),daf-16基因的mRNA表达水平上调(P<0.05),并上调其下游靶基因sod-3、clk-2的mRNA表达,以及下调ctl-1、dod-17的mRNA表达(P<0.05)。50 mmol/L阿魏酸处理后DAF-16::GFP在细胞核定位的线虫比例从(5.3±1.5)%增加到(28±3)%。daf-2(DR1572)、daf-16(CF1038)突变体线虫在50 mmol/L阿魏酸处理后,寿命未见明显延长(P>0.05)。【结论】阿魏酸可通过胰岛素/IGF信号通路,促进DAF-16的核定位,提高机体应激抵抗能力,并延长线虫寿命。【Objective】To investigate the effect on life extension and the mechanism of ferulic acid in Caenorhabditis elegans.【Methods】We used C.elegans as an anti-aging model,and different concentrations of ferulic acid(0,1,10,50 mmol/L)were given to explore its regulatory effects on the lifespan,anti-stress ability,and lipofuscin level ofC.elegans.And we used qPCR to screen senescence related genes,and DAF-2(DR1572)and DAF-16(CF1038)mutants were used to investigate the potential mechanism of ferulic acid.【Results】Compared with the blank control group,ferulic acid significantly extended the lifespan of C.elegans and increased its antioxidant and thermal stress(P<0.001),inhibited the accumulation of lipofuscin related to aging(P<0.001),and did not affect its fertility and body shape(P>0.05).After feeding nematode in the 50 mmol/L ferulic acid group,mRNA expression levels of DAF-2,Akt-2 and AGE-1 genes were down-regulated(P<0.05),mRNA expression levels of DAF-16 genes were up-regulated(P<0.05)and the expression levels of its downstream target genes sod-3,ctl-1,clk-2 and dod-17 were activated(P<0.05).After 50 mmol/L ferulic acid treatment,the proportion of daf-16::GFP in the nematode cell nucleus increased from(5.3±1.5)%to(28±3)%.The lifespan of DAF-2(DR1572)and DAF-16(CF1038)mutant nematodes was not significantly extended after treat⁃ment with 50 mmol/L ferulic acid(P>0.05).【Conclusions】Ferulic acid can promote the nuclear localization of daf-16 through insulin/IGF signaling pathway,improve the stress resisting ability of the organism,and prolong the lifespan of nematode.

关 键 词：阿魏酸 胰岛素/IGF信号通路 DAF-16 衰老 秀丽隐杆线虫 

分 类 号：R592[医药卫生—老年医学]