Lee Jiyun, Kwon Gayeung, Park Jieun, Kim Jeong-Keun, Lim Young-Hee
Department of Public Health Science (Brain Korea 21 PLUS program), Graduate School, Korea University, Seoul 136-701, Republic of Korea.
Department of Chemical Engineering and Biotechnology, Korea Polytechnic University, Shihung-si, Gyeonggi-do 429-793, Republic of Korea.
Exp Biol Med (Maywood). 2016 Oct;241(16):1757-63. doi: 10.1177/1535370216650054. Epub 2016 May 10.
Resveratrol (RES) has been studied for its effects on the lifespan extension of Caenorhabditis elegans, but controversy still remains on its mechanism related with SIR-2. In this study, longevity assay was performed to confirm SIR-2-dependent lifespan extension of C. elgeans with RES and oxyresveratrol (OXY), an isomer of hydroxylated RES using loss-of-function mutants of C. elegans including sir-2.1 mutant. The results showed that OXY and RES significantly (P < 0.05) extended the lifespan of C. elegans compared with the control. OXY and RES also significantly (P < 0.05) increased the mRNA expression levels of sir-2.1 and aak-2 in a dose-dependent manner and increased the protein expression levels of SIR-2.1. OXY and RES treatment extended the lifespan in daf-16 loss-of-function mutants, which suggested that lifespan extension was not occurring via the activation of DAF-16. However, OXY and RES failed to extend the lifespan in loss-of-function mutants of sir-2.1 and aak-2 Therefore, OXY and RES extend the lifespan of C. elegans by overexpression of SIR-2.1, which is related to lifespan extension through calorie restriction and the AMP-activated protein kinase (AMPK) pathway, although this process is independent of the FOXO/DAF-16 pathway.
白藜芦醇(RES)对秀丽隐杆线虫寿命延长的影响已得到研究,但在其与SIR-2相关的机制方面仍存在争议。在本研究中,进行了寿命测定,以使用包括sir-2.1突变体在内的秀丽隐杆线虫功能丧失突变体,来确认RES和氧化白藜芦醇(OXY,RES的羟基化异构体)对秀丽隐杆线虫SIR-2依赖性的寿命延长作用。结果表明,与对照组相比,OXY和RES显著(P < 0.05)延长了秀丽隐杆线虫的寿命。OXY和RES还以剂量依赖性方式显著(P < 0.05)提高了sir-2.1和aak-2的mRNA表达水平,并提高了SIR-2.1的蛋白质表达水平。OXY和RES处理延长了daf-16功能丧失突变体的寿命,这表明寿命延长不是通过激活DAF-16发生的。然而,OXY和RES未能延长sir-2.1和aak-2功能丧失突变体的寿命。因此,OXY和RES通过过表达SIR-2.1延长了秀丽隐杆线虫的寿命,这与通过热量限制和AMP激活的蛋白激酶(AMPK)途径延长寿命有关,尽管这个过程独立于FOXO/DAF-16途径。