Length of paternal lifespan is manifested in the DNA methylome of their nonagenarian progeny

// Saara Marttila 1,2 , Laura Kananen 1,2 , Juulia Jylhava 1,2 , Tapio Nevalainen 1,2 , Antti Hervonen 2,3 , Marja Jylha 2,3,4 and Mikko Hurme 1,2,5 1 Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland 2 Gerontology Research Center, Tampere, Finland 3 School of Health Sciences, University of Tampere, Tampere, Finland 4 Institute for Advanced Social Research, University of Tampere, Tampere, Finland 5 Fimlab Laboratories, Tampere, Finland Correspondence to: Saara Marttila, email: // Keywords : lifespan, longevity, DNA methylation, methylome, intergenerational inheritance, Gerotarget Received : August 17, 2015 Accepted : August 27, 2015 Published : September 30, 2015 Abstract The heritability of lifespan is 20-30%, but only a few genes associated with longevity have been identified. To explain this discrepancy, the inheritance of epigenetic features, such as DNA methylation, have been proposed to contribute to the heritability of lifespan. We investigated whether parental lifespan is associated with DNA methylation profile in nonagenarians. A regression model, adjusted for differences in blood cell proportions, identified 659 CpG sites where the level of methylation was associated with paternal lifespan. However, no association was observed between maternal lifespan and DNA methylation. The 659 CpG sites associated with paternal lifespan were enriched outside of CpG islands and were located in genes associated with development and morphogenesis, as well as cell signaling. The largest difference in the level of methylation between the progeny of the shortest-lived and longest-lived fathers was identified for CpG sites mapping to CXXC5 . In addition, the level of methylation in three Notch-genes ( NOTCH1 , NOTCH3 and NOTCH4 ) was also associated with paternal lifespan. There are implications for the inheritance of acquired traits via epigenetic mechanisms in mammals. Here we describe DNA methylation features that are associated with paternal lifespan, and we speculate that the identified CpG sites may represent intergenerational epigenetic inheritance.