DNA-DAMAGE AND REPAIR IN TELOMERES - RELATION TO AGING

We have established a method for the detection of DNA damage and its r epair in human telomeres, the natural ends of chromosomes which are ne cessary for replication and critical for chromosomal stability. We fin d that ultraviolet light-induced pyrimidine dimers in telomeric DNA ar e repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric len gth, telomeric DNA damage, and its repair in relation to the progressi on of aging. Telomeres are shorter in fibroblasts from an old donor co mpared to fibroblasts from a young donor, shortest in cells from a pat ient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA re pair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werne r cells. It is possible that this decline in telomeric repair with agi ng is of functional significance to an age-related decline in genomic stability.