Jan Hoeijmakers joined the Dept. of Genetics of the Erasmus University in Rotterdam in 1981 to work on DNA repair. His team succeeded in cloning the first of many subsequent human DNA-repair genes allowing elucidation of the reaction mechanism of nucleotide excision repair, discovered the strong evolutionary conservation of DNA repair, resolved the basis of a variety of enigmatic human repair syndromes and identified a new class of ‘basal transcription disorders’. His laboratory generated a comprehensive series of mouse DNA repair mutants, strikingly mimicking the corresponding human syndromes, which provided detailed insight into the complex etiology of human repair diseases. He discovered a very strong, initially highly controversial connection between DNA damage and (bona fide) aging, and on this basis proposed a trade-off between cancer and aging. By modulating DNA repair, damage induction and nutrition my team succeeded in largely controlling the process of aging in mice. The type of DNA repair defect is found to determine the type of segmental accelerated aging and/or cancer. The severity of DNA repair deficiency correlates with the rate of accelerated aging: shortening lifespan and time of onset of many aging-related diseases from years to weeks.