Differential Gene Expression Patterns between Young and Old Human Fibroblasts under Oxidative Stress

            Yi-Shing Ma and Yau-Huei Wei

Department of Biochemistry, National Yang-Ming University, Taipei 112, Taiwan


Increasing attention has been paid on the hypothesis that free radicals and oxidative stress play a role in cellular and organismal aging.  To uncover genes responsible for differential response to oxidative stress between young and old human skin fibroblasts, we examined differences in gene expression patterns revealed by cDNA microarray analysis and compared these changes with those caused by sublethal dose of H2O2.  Some of these differentially expressed genes in human fibroblasts under oxidative stress were then confirmed by RT-PCR.  We found that the expressions of the growth arrest-related and DNA damage (GADD) inducible gene 45 and GADD153 and transcription factor ETR101 are up-regulated by 180 mM H2O2 in both young and old fibroblasts.  Concurrent with these events is the induction of growth arrest genes, which may play an important role in the response of cells to DNA damage elicited by oxidative stress.  On the other hand, a set of genes including human early growth response protein 1 (hEGR1), an ''immediate-early'' gene that is believed to link extracellular mitogenic signals to cell-cycle progression, are induced significantly in old fibroblasts but are suppressed in young fibroblasts upon exposure to 180 mM H2O2.  We also found that the basal level of the hEGR1 transcript in old fibroblasts is lower than that in young fibroblasts.  The results of microarray analysis suggest that these aging-associated differentially expressed genes play an important role for human fibroblasts to cope with oxidative stress, and that an alteration in the activity and capacity of this stress response system contributes to human aging