THE EFFECT OF DONOR AGE ON THE PROCESSING OF UV-DAMAGED DNA BY CULTURED HUMAN-CELLS - REDUCED DNA-REPAIR CAPACITY AND INCREASED DNA MUTABILITY

Aging in humans carries an increased risk of skin cancer, a disorder l inked to somatic mutations in sun damaged skin. DNA repair plays a maj or role in protection against sun damage. We found an age-related decl ine in post-UV DNA repair capacity (measured by the ability to repair a W-treated plasmid (pCMVcat)) of -0.6% per year (p = 0.0001) in cultu red primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase i n post-UV mutability (measured as mutations introduced into a transfec ted, UV-treated plasmid (pSP189)) of + 0.6% per year (p = 0.001) in ly mphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ab ility to process new UV-induced DNA damage and this age-related reduct ion in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells.