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

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 g0/g1 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 g0/g1 phase and increased cell populations in the g2/m phase. γ-tocotrienol treatment also upregulated eln and col1a1 and downregulated mmp1 and il6 expression in young and senescent fibroblasts. conclusion: 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.