title: Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts.
abstract: OBJECTIVE
  Human diploid fibroblasts undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular aging. The beneficial effects of vitamin E in aging have been established, but studies to determine the mechanisms of these effects are ongoing. This study determined the molecular mechanism of γ-tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human diploid fibroblasts using the expression of senescence-associated genes.
  
  
  METHODS
  Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.
  
  
  RESULTS
  The cell cycle was arrested in the G(0)/G(1) phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.
  
  
  CONCLUSIONS
  γ-Tocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.
authors.affiliation: Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Biochemistry, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia. suzanamakpol@yahoo.com
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
authors.forename: Azalina
authors.initials: A
authors.lastname: Zainuddin
authors.forename: Kien Hui
authors.initials: KH
authors.lastname: Chua
authors.forename: Yasmin Anum Mohd
authors.initials: YA
authors.lastname: Yusof
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
mesh_terms: D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D002839:Chromans / Q000494:pharmacology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D001616:beta-Galactosidase / Q000032:analysis* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; C530104:CCND1 protein, human; D002839:Chromans; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D015850:Interleukin-6; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D014810:Vitamin E; C013649:plastochromanol 8; D001616:beta-Galactosidase; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1