Mechanisms and implications of the age-associated decrease in DNA repair capacity

Skin cancer incidence is clearly linked to UV irradiation and increases exp onentially with age, We studied the rate of removal of thymine dimers and ( 6-4) photoproducts in UV-irradiated human dermal fibroblasts derived from d onors of different ages. There was a significant decrease with aging in the repair rates of both thymine dimers and (6-4) photoproducts. (P<0.001). In addition, there was an age-associated decrease in the protein levels of ER CC3, PCNA, RPA, XPA, and p53 that participate in nucleotide excision repair . Moreover, the mRNA levels of XPA, ERCC3, and PCNA were significantly redu ced with aging, suggesting that these decreases are often regulated at the mRNA level. Furthermore, with age induction of p53 after UV irradiation was significantly reduced. Taken together, our data suggest that the age-assoc iated decrease in the repair of UV-induced DNA damage results at least in p art from decreased levels of proteins that participate in the repair proces s.