Of the three categories of solar UV radiation, only UV-A and UV-B are able to penetrate Earth's atmosphere. Thus, these two types of UV radiation are of greatest concern to humans. UV radiation causes two classes of DNA lesions: cyclobutene pyrimidine dimers and 6-4 photoproducts. Both of these lesions distort DNA's structure, introducing bends or kinks and thereby impeding transcription and replication.
Evidence is presented that damage to nuclear DNA (nDNA) is a direct cause of aging in addition to the effects of nDNA damage on cancer, apoptosis, and cellular senescence. Many studies show significant nDNA damage with age, associated with declining nDNA repair. Evidence for decline of nDNA repair with age is reviewed. Mammalian lifespans correlate with effectiveness of nDNA repair. The most severe forms of accelerated aging disease in humans are due to nDNA repair defects, and many of these diseases do not exhibit increased cancer incidence. High rates of cellular senescence and apoptosis due to high rates of nDNA damage are apparently the main cause of the elderly phenotype in these diseases. Transgenic mice with high rates of cellular senescence and apoptosis exhibit an elderly phenotype, whereas some strains with low rates of cellular senescence and apoptosis show extended lifespan. Age-associated increases of nDNA damage in the brain may be problematic for rejuvenation because neurons may be difficult to replace and artificial nDNA repair could be difficult.
