Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging

In this study, we assessed global gene expression patterns in adolescent mice exposed to lead (Pb) as infants and their aged siblings to identify reprogrammed genes. Global expression on postnatal day 20 and 700 was analyzed and genes that were down- and up-regulated (≥2 fold) were identified, clustered and analyzed for their relationship to DNA methylation. About 150 genes were differentially expressed in old age. In normal aging, we observed an up-regulation of genes related to the immune response, metal-binding, metabolism and transcription/transduction coupling. Prior exposure to Pb revealed a repression in these genes suggesting that disturbances in developmental stages of the brain compromise the ability to defend against age-related stressors, thus promoting the neurodegenerative process. Overexpression and repression of genes corresponded with their DNA methylation profile.

► Early-life exposure to a pollutant reprograms global gene expression in old age through epigenetic mechanisms. ► Genes associated with the immune response, metal binding, metabolism and transcription are up-regulated in the aging brain. ► Developmental exposure to a pollutant (Pb) results in the repression of these genes in old age. ► Reprogrammed gene expression appears to correlate with alterations in DNA methylation.