Some correlations have been reported between DNA repair mechanisms and longevity in mammals. It has been argued, however, that such correlations may be an artefact of longlived species being on average bigger since, independently of lifespan, larger animals are expected to have higher DNA repair rates. Whilst earlier studies focused on NER, more recent studies have focused on BER, though results have been mixed. To test the hypothesis that PARP optimization contributed to the evolution of longevity, mice with human PARP ectopically expressed were generated, though it resulted in impaired DNA repair and a short lifespan. Of course, because DNA repair is a complex process, it could be that ectopic expression of PARP disrupted the ne balance of DNA repair proteins, disrupting DNA repair.Because DNA repair systems tend to be largely conserved evolutionary, it could also be that species differences in ageing are due to the way cells respond to DNA damage.This could involve cell decisions on how to repair the damage or even decisions at the level of whether to repair the damage or let the damaged cell die.There are complex pathways affecting these decisions and these may be involved in species differences in ageing.We speculate that shortlived species, which tend to grow fast, would favour responses that optimize growth even if that leads to a buildup of damaged cells and consequently a higher cancer incidence and a faster ageing process later in life.On the other hand, longerlived species can afford to eliminate damaged cells and grow slower, resulting in a slower buildup of damage, lower cancer incidence and slower ageing.According to this model, tradeoffs in the evolution of DNA damage responses would be important for species differences in ageing rather than DNA repair per se.Studies of longlived mammalian species are necessary to address these questions and identify the specic cellular, genetic and molecular mechanisms involved in species differences in ageing and cancer.One emerging model in ageing research is the naked molerat. These mechanisms combine processes for assuring that the DNA of each cell is maintained unchanged and replacing genomes damaged beyond a given threshold by cell selfdestruction mechanisms.It is equally clear that DNA changes accumulate with age in multiple tissues and are likely to contribute to the increased cancer incidence observed with age, even though which DNA lesions are more important contributors to broader aspects of ageing remains unknown.One major hypothesis is that DNA damage activates signalling pathways that, perhaps through cell function disruption or cell loss, result in a depletion of stem cell stocks which then contributes to ageing.As such, the idea that DNA damage accumulation with age is the primary cause of ageing remains an intuitive and powerful one.Human progeroid syndromes clearly show that disruption of DNA repair pathways can accelerate the ageing phenotype.Although it is not clear how representative of normal ageing the changes observed in progeroid syndromes are, the breadth of agerelated changes observed prematurely in certain progeroid syndromes suggests that at least some aspects of ageing are the same.The fact that disruption of DNA repair can accelerate ageing is not proof by itself that DNA damage causes ageing but remains a strong argument.