Affymetrix gene-expression analysis was performed on mRNAs from involved and noninvolved skin biopsies from three volunteers with Lentigo senilis. Of the 42,000 transcripts scanned, 17 were downregulated (<1.4 times below the control level) and 23 were upregulated (>1.9 times above the control level). A serine peptidase gene was downregulated in keeping with the suggestion that age spots are associated with impaired melanin degradation. Three genes involved in the keratinization and synthesis and the organization of fibers in the basement membrane were downregulated, two metalloproteinase genes were upregulated, as were six genes associated with the inflammatory response, in keeping with the postulate that the visible aspects of aged skin are causally linked with a microinflammatory response. The regulation of five genes associated with the Wnt family was altered. Antiapoptotic genes were downregulated, and six genes associated with transmembrane transport were upregulated.