MPK-1/ERK is required for the full activity of resveratrol in extended lifespan and reproduction

Dong Suk Yoon, Dong Seok Cha, Yoorim Choi, Jin Woo Lee, Myon Hee Lee

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere12867
JournalAging Cell
Volume18
Issue number1
DOIs
Publication statusPublished - 2019 Feb 1

Bibliographical note

Funding Information:
National Institutes of Health, Grant/Award Number: AG060373; National Research Foundation of Korea, Grant/Award Number: the Basic Science Research Program / NRF-2014R1A6A

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Ageing
  • Cell Biology

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