Open AccessMPK‐1/ERK is required for the full activity of resveratrol in extended lifespan and reproduction
Author(s) -
Yoon Dong Suk,
Cha Dong Seok,
Choi Yoorim,
Lee Jin Woo,
Lee MyonHee
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12867
Subject(s) - longevity , biology , caenorhabditis elegans , sirtuin , germline , resveratrol , mutant , model organism , drosophila melanogaster , rna interference , microbiology and biotechnology , genetics , gene , rna , biochemistry , acetylation
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.