Research Paper Volume 3, Issue 11 pp 1098—1109

Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor

Lan Xiang1,3,5, , Yukiko Nakamura3, , Young-Mi Lim2, , Yasutoyo Yamasaki2, , Yumi Kurokawa-Nose1, , Wakako Maruyama1, , Toshihiko Osawa3, , Akira Matsuura4, , Noboru Motoyama1, , Leo Tsuda2, ,

  • 1 Department of Cognitive Brain Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan
  • 2 Animal Models of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan
  • 3 Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • 4 Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba 263-8522, Japan
  • 5 Current address: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310029, China

Received: November 1, 2011       Accepted: December 6, 2011       Published: December 8, 2011
How to Cite

Copyright: © 2011 Xiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The O-type forkhead domain transcription factor (FOXO) is involved in many biological processes such as aging, the oxidative stress response, and growth regulation. FOXO activity is tightly controlled within cells. In particular, growth factor signaling pathways and the oxidative stress response can both stimulate nuclear translocation of this transcription factor. Here, we show that tetrahydrocurcumin (THC), a curcumin metabolite, regulates the oxidative stress response and aging via FOXO. In NIH3T3 cells, THC induced nuclear accumulation of FOXO4, a member of the FOXO family of transcription factors, by inhibiting phosphorylation of protein kinase B (PKB)/Akt. In Drosophila melanogaster, THC attenuated the oxidative stress response, an effect that was blocked in a foxo mutant background. THC also extended the life span of Drosophila under normal conditions, and loss of either foxo or Sir2 activity eliminated this effect. Based on these results, THC may regulate the aging process via an evolutionarily conserved signaling pathway that includes both foxo and Sir2.


THC: tetrahydrocurcumin; C: curcumin; ROS: reactive oxygen species; FOXO: O-type forkhead domain transcription factor; MnSOD: Mn superoxide dismutase; RES: resveratrol; DAPI: 4′,6-diamidino-2-phenylindole dihydrochloride; CR: caloric restriction; PKB: protein kinase B); IGF: insulin growth factor.