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 linked to somatic mutations in sun damaged skin. DNA repair plays a major role in protection against sun damage. We found an age-related decline in post-UV DNA repair capacity (measured by the ability to repair a UV-treated plasmid (pCMVcat)) of-0.6% per year (p = 0.0001) in cultured primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase in post-UV mutability (measured as mutations introduced into a transfected, UV-treated plasmid (pSP189)) of +0.6% per year (p = 0.001) in lymphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ability to process new UV-induced DNA damage and this age-related reduction in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells.
Moriwaki
S
S
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ray
S
S
Tarone
R E
RE
Kraemer
K H
KH
Grossman
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D011088:DNA Ligases / Q000302:isolation & purification / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008875:Middle Aged; D016296:Mutagenesis; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004268:DNA-Binding Proteins; D011088:DNA Ligases