Brief Communication: SIR-2.1-dependent lifespan extension of Caenorhabditis elegans by oxyresveratrol and resveratrol

Abstract

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.

Keywords: Caenorhabditis elegans; Oxyresveratrol; SIR-2.1; lifespan; resveratrol.

Figure 1

Effect of RES or OXY on Caenorhabditis elegans (N2) lifespan. After 3 days of feeding with Escherichia coli OP50 on NGM plates, young adult worms were transferred to NGM/FUdR plates seeded with E. coli OP50 and containing RES (a) or OXY (b). The lifespans of nematodes fed on NGM/FUdR plates containing RES or OXY were significantly (P < 0.05) extended compared to those fed on NGM/FUdR plates containing DMSO only

Figure 2

Changes in gene expression and SIR-2.1 protein expression of Caenorhabditis elegans (N2) fed on NGM/FUdR plates containing RES or OXY. The expression level of the genes was used to evaluate the effect of RES and OXY on the lifespan of C. elegans (a). Western blot was conducted to investigate the effect of OXY on SIR-2.1 protein expression (b, c). The expression level of SIR-2.1 protein significantly increased in the 1000 µM RES and 100, 500, and 1000 µM OXY groups, as compared with the control, in a dose-dependent manner. Asterisks denote significant differences compared with worms fed on NGM/FUdR plates containing DMSO only. *P < 0.05; **P < 0.01; ***P < 0.001