Down-Regulation of Nuclear Binding Activities of OXBOX-REBOX Transcription Factors during Cellular Senescence

Abstract Functional capacity of mitochondria declines during aging and this impairment may have a major role in aging process. Several observations indicate that transcriptional efficiency is reduced during aging. Our purpose was to find out whether aging and cellular senescence affect the nuclear binding activities of transcription factors which bind to OXBOX-REBOX sequence present in promoter regions of numerous nuclear genes encoding mitochondrial proteins. These factors regulate and coordinate the expression of mitochondrial proteins. We observed a strong down-regulation in the nuclear binding activities of OXBOX-REBOX factors in replicatively senesced human WI-38 and IMR-90 fibroblasts. On the contrary, SV-40 immortalization highly increased the nuclear binding activities. A considerable down-regulation of OXBOX-REBOX factors was also observed in UVB-irradiated WI-38 fibroblasts. Irradiation induced photoaging in fibroblasts which involved cell cycle arrest and senescent morphology. Interestingly, the nuclear binding activities of OXBOX-REBOX factors were also prominently decreased in the liver of Wistar rats at the age of 30 months but not yet at the age of 18 months. Our results suggest that the down-regulation of OXBOX-REBOX factors could affect the expression level of mitochondrial proteins encoded in nucleus and hence induce disturbances in mitochondrial function and promote the cellular aging process.