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Human progeroid syndromes are caused by mutations in single genes accelerating some but not all features of normal aging. Most progeroid disorders are linked to defects in genome maintenance, and while it remains unknown if similar processes underlie normal and premature aging, they provide useful models for the study of aging. Altered transcription is speculated to play a causative role in aging, and is involved in the pathology of most if not all progeroid syndromes. Previous studies demonstrate that there is a similar pattern of gene expression changes in primary cells from old and Werner syndrome compared to young suggesting a presence of common cellular aging mechanisms in old and progeria. Here we review the role of transcription in progeroid syndromes and discuss the implications of similar transcription aberrations in normal and premature aging.

Cockayne syndrome (CS) is a human hereditary disease belonging to the group of segmental progerias, and the clinical phenotype is characterized by postnatal growth failure, neurological dysfunction, cachetic dwarfism, photosensitivity, sensorineural hearing loss, and retinal degradation. CS-B cells are defective in transcription-coupled DNA repair, base excision repair, transcription, and chromatin structural organization. Using array analysis, we have examined the expression profile in CS complementation group B (CS-B) fibroblasts after exposure to oxidative stress (H2O2) before and after complete complementation with the CSB gene. The following isogenic cell lines were compared: CS-B cells (CS-B null), CS-B cells complemented with wild-type CSB (CS-B wt), and a stably transformed cell line with a point mutation in the ATPase domain of CSB (CS-B ATPase mutant). In the wt rescued cells, we detected significant induction (two-fold) of 112 genes out of the 6912 analysed. The patterns suggested an induction or upregulation of genes involved in several DNA metabolic processes including DNA repair, transcription, and signal transduction. In both CS-B mutant cell lines, we found a general deficiency in transcription after oxidative stress, suggesting that the CSB protein influenced the regulation of transcription of certain genes. Of the 6912 genes, 122 were differentially regulated by more than two-fold. Evidently, the ATPase function of CSB is biologically important as the deficiencies seen in the ATPase mutant cells are very similar to those observed in the CS-B-null cells. Some major defects are in the transcription of genes involved in DNA repair, signal transduction, and ribosomal functions.