The gene expression profiles of lysophosphatidic acid (LPA)-treated young and senescent human diploid fibroblasts (HDFs) were examined using cDNA microarray analysis. The expression of some genes, including EGR 1/3 and MRRF, was controlled by LPA similarly in young and senescent cells, showing a typical time-dependent up-and-down expression profile. In contrast, some other genes, including DUSP6, CYR61, and F3, showed sustained upregulation in senescent HDFs later after LPA treatment. These genes might be involved in altered LPA responsiveness during the aging process.