Fragile X syndrome is caused due to silencing of FMR-1 gene transcription leading to loss of fragile X mental retardation protein (FMRP). To investigate whether the transcriptional mechanism is linked to aging, we have studied interaction of the transcription factors USF1/USF2 and alpha-Pal/Nrf1 to E-box and GC-box, respectively, in Fmr-1 promoter in the brain of young, adult, and old mouse using electrophoretic mobility shift assay (EMSA). Our data reveal that the interaction of these transcription factors to their respective promoter sequences increases in mouse brain as a function of age. The finding on the interaction of the above transcription factors to their cognate sequences is novel as the Current investigation has been carried out in intact and aging mouse. The present finding is important in respect to age- and FMRP-dependent brain function. (C) 2008 Elsevier Inc. All rights reserved.