title: Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways.
abstract: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).
  
  
  
  Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.
  
  
  
  Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.
  
  
  
  Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.
authors.affiliation: Department of Biochemistry, Level 17, Pre-Clinical Building, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: S C
authors.initials: SC
authors.lastname: Khor
authors.affiliation: Department of Biochemistry, Level 17, Pre-Clinical Building, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Y A
authors.initials: YA
authors.lastname: Mohd Yusof
authors.affiliation: Department of Biochemistry, Level 17, Pre-Clinical Building, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wan Ngah
authors.affiliation: Department of Biochemistry, Level 17, Pre-Clinical Building, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: S
authors.initials: S
authors.lastname: Makpol
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D024508:Tocotrienols / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D024508:Tocotrienols; D014810:Vitamin E
keywords: Cellular aging; Gene expression; Human diploid fibroblasts; Tocotrienol-rich fraction; Vitamin E