Association between genome-wide DNA methylation and all-cause mortality in nonagenarians. Homo sapiens

Changes in the DNA methylation (DNAm) landscape have been implicated in aging and cellular senescence. To unravel the role of specific DNAm patterns in late-life survival, we performed genome-wide methylation profiling in nonagenarians (n=111) and determined the performance of the methylomic predictors and conventional risk markers in a longitudinal setting. The survival model containing only the methylomic predictors was superior in terms of predictive accuracy compared with the models containing the conventional predictors body mass index and mini-mental state examination. At the 2.55-year follow-up, we identified 19 mortality-associated (false-discovery rate <0.5) CpG sites that mapped to genes functionally clustering around the nuclear factor kappa B (NF-κB) complex. Interestingly, none of the mortality-associated CpG sites overlapped with the established aging-associated DNAm sites. Our results are in line with previous findings on the role of NF-κB in controlling animal life spans and demonstrate the key role of this complex in human longevity. Overall design: Bisulphite converted DNA from 122 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip