Resveratrol (RSV) extends the lifespan of various organisms through activation of sirtuin. However, whether RSV-mediated longevity is entirely dependent upon sirtuin is still controversial. Thus, understanding additional mechanisms concerning the genetic requirements for the biological activity of RSV needs to be clarified to utilize the beneficial effects of RSV. In this study using Caenorhabditis elegans as a model system, we found that MPK-1 (an ERK homolog) signaling is necessarily required for RSV-mediated longevity of sir-2.1/sirtuin mutants as well as for wild-type worms. We demonstrated that MPK-1 contributes to RSV-mediated longevity through nuclear accumulation of SKN-1 in a SIR-2.1/DAF-16 pathway-independent manner. The positive effect of RSV in regulating lifespan was completely abolished by RNA interference against mpk-1 in the sir-2.1 and daf-16 mutants, strongly indicating that the MPK-1/SKN-1 pathway is involved in RSV-mediated longevity, independently of SIR-2.1/DAF-16. We additionally found that RSV protected worms from oxidative stress via MPK-1. In addition to organismal aging, RSV prevented the age-associated loss of mitotic germ cells, brood size, and reproductive span through MPK-1 in C. elegans germline. Therefore, our findings not only provide new mechanistic insight into the controversial effects of RSV on organismal longevity, but additionally have important implications in utilizing RSV to improve the outcome of aging-related diseases.
Bibliographical noteFunding Information:
National Institutes of Health, Grant/Award Number: AG060373; National Research Foundation of Korea, Grant/Award Number: the Basic Science Research Program / NRF-2014R1A6A
We thank Professor T. Keith Blackwell (Harvard Medical School) for the LD1 (ldIs7 [skn‐1b/c::GFP + rol‐6(su1006)]) strain. This work was supported by NIH (AG060373) to M‐HL and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐ 2014R1A6A3A01053793) to DSY.
All Science Journal Classification (ASJC) codes
- Cell Biology