Gamma-tocotrienol modulation of senescenceassociated gene expression prevents cellular aging in human diploid fibroblasts

Suzana Makpol, Azalina Zainuddin, Chua Kien Hui, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. CONCLUSION: γTocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalClinics
Volume67
Issue number2
DOIs
Publication statusPublished - 2012

Fingerprint

Cell Aging
Tocotrienols
Diploidy
Fibroblasts
Gene Expression
Interleukin-6
Cell Cycle
Vitamin E
plastochromanol 8
S Phase
Cell Division
Population
Genes
Real-Time Polymerase Chain Reaction
Up-Regulation
Down-Regulation
Growth

Keywords

  • Cellular aging
  • Human diploid fibroblasts
  • Molecular mechanism
  • Senescence-associated genes
  • Vitamin e

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gamma-tocotrienol modulation of senescenceassociated gene expression prevents cellular aging in human diploid fibroblasts. / Makpol, Suzana; Zainuddin, Azalina; Kien Hui, Chua; Mohd Yusof, Yasmin Anum; Ngah, Wan Zurinah Wan.

In: Clinics, Vol. 67, No. 2, 2012, p. 135-143.

Research output: Contribution to journalArticle

Makpol, Suzana ; Zainuddin, Azalina ; Kien Hui, Chua ; Mohd Yusof, Yasmin Anum ; Ngah, Wan Zurinah Wan. / Gamma-tocotrienol modulation of senescenceassociated gene expression prevents cellular aging in human diploid fibroblasts. In: Clinics. 2012 ; Vol. 67, No. 2. pp. 135-143.
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N2 - 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. CONCLUSION: γTocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.

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