CONCLUSION

In this study, we investigated the association between human longevity and genetic variation in nine sub-processes of DNA damage response and repair, all considered to have key roles in maintenance of genetic stability and the aging process. We observed significant support for an association of the entire pathway with longevity. In the competitive analysis, we found BER, HRR, and RECQ to be nominally significantly more associated with longevity than other sub-processes. However, this did not remain significant in general. An intriguing aspect of human longevity is the difference in survival which has been suggested to have a genetic basis. A sex-stratified self-contained based analysis of all SNPs investigated showed significance for BER. The association was caused by several genes indicating that variation in BER might influence longevity more than other sub-processes.

Still, as these findings did not show replication in the German study population, more analyses are needed in additional study populations before a final conclusion can be drawn.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

ACKNOWLEDGEMENTS

This study was supported by the Max-Planck Institute for Demographic Research (Rostock, Germany), the INTERREG 4 A programme Syddanmark Schleswig-K.E.R.N, the European Regional Development Fund, the European Union's Seventh Framework Programme (FP7/20072011) under grant agreement no. 259679, the National Institute on Aging (P01 AG08761), the RESOLVE project (FP7-HEALTH-F4-2008-202047), and the Novo Nordisk, the Aase and Ejnar Danielsen, the Brdrene Hartmann, the King Christian the 10th and the Einer Willumsens Mindelegat Foundations. The Danish Aging Research Center is supported by a grant from the VELUX Foundation, while Mette Soerensen is supported by an individual postdoctoral grant from The Danish Council for Independent Research Medical Sciences.

A population-based study of Danish twin pairs born in 1870-1900 showed that genetic factors have a significant influence on human lifespan and longevity. The quest for genetic determinants of human longevity is challenging but insights have been gained from investigating DNA damage response and repair mechanisms. DNA repair deficiency has been associated with neurodegeneration and aging. Telomere length predicts survival independent of genetic influences. Free radicals and oxidative damage are also implicated in aging.http://www.nature.com/ejhg