title: Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor.
abstract: 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.
authors.affiliation: Department of Cognitive Brain Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiang
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lim
authors.forename: Yasutoyo
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kurokawa-Nose
authors.forename: Wakako
authors.initials: W
authors.lastname: Maruyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Osawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuura
authors.forename: Noboru
authors.initials: N
authors.lastname: Motoyama
authors.forename: Leo
authors.initials: L
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004331:Drosophila melanogaster; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007150:Immunohistochemistry; D008017:Life Expectancy; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; C096277:tetrahydrocurcumin; D003474:Curcumin