Marttila Saara, Kananen Laura, Jylhävä Juulia, Nevalainen Tapio, Hervonen Antti, Jylhä Marja, Hurme Mikko
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.
Gerontology Research Center, Tampere, Finland.
Oncotarget. 2015 Oct 13;6(31):30557-67. doi: 10.18632/oncotarget.5905.
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.
寿命的遗传度为20%-30%，但仅鉴定出少数与长寿相关的基因。为了解释这一差异，有人提出表观遗传特征（如DNA甲基化）的遗传有助于寿命的遗传度。我们调查了百岁老人的父母寿命是否与DNA甲基化谱相关。一个针对血细胞比例差异进行调整的回归模型，确定了659个CpG位点，其甲基化水平与父亲的寿命相关。然而，未观察到母亲寿命与DNA甲基化之间的关联。与父亲寿命相关的659个CpG位点在CpG岛之外富集，位于与发育、形态发生以及细胞信号传导相关的基因中。在映射到CXXC5的CpG位点上，寿命最短和最长的父亲的后代之间甲基化水平差异最大。此外，三个Notch基因（NOTCH1、NOTCH3和NOTCH4）的甲基化水平也与父亲寿命相关。这对哺乳动物通过表观遗传机制遗传获得性性状具有启示意义。在此，我们描述了与父亲寿命相关的DNA甲基化特征，并推测所鉴定的CpG位点可能代表代际表观遗传遗传。
