Effects of aging on gene specific repair

DNA in cells is constantly exposed to insults from both endogenous and exogenous factors that may cause breaks in the phosphodiester backbone, cleavage of N -glycosylic bonds, alteration of structure of the purine or pyrimidine bases, intrastrand or interstrand crosslinks, and distortion of helix by intercalation. The age-related decrease in the ability of the cells to repair non-transcribed, silent regions of the DNA could play a role in the age-related accumulation of DNA damage and mutations, which occur with increasing age. The results from several studies suggest that chromatin becomes more condensed with age because of an increase in protein-DNA cross-links and internucleosome interaction. The chromatin template activity for α and β-DNA polymerases declines with age. This age-related change is due to an increased chromosomal condensation. Increased chromosomal condensation could also reduce the access of DNA repair proteins to the DNA and thereby decrease the repair of the lesions. The potential importance of the age-related decrease in preferential repair in aging is also illustrated by a genetic disease, Cockayne's syndrome. This disease is associated with a loss of preferential repair of the transcribed strand of transcriptionally active genes.