Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging.
There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age-and the deviation of chronological and predicted age (∆age) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy.



In the German ESTHER cohort, we used 864 DNAm profiles of blood samples as the discovery set and 1000 DNAm profiles as the validation set to predict chronological age with three previously reported age predictors-based on 99, 71, or 353 age-associated CpGs. Several of these individual CpGs were significantly associated with life expectancy, and for some of these CpGs, this was even reproducible in the independent datasets. Notably, those CpGs that revealed significant association with life expectancy were overall rather hypomethylated upon aging.



Individual age-associated CpGs may provide biomarkers for all-cause mortality-but confounding factors need to be critically taken into consideration, and alternative methods, which facilitate more quantitative measurements at individual CpGs, might be advantageous. Our data suggest that particularly specific CpGs that become hypomethylated upon aging are indicative of biological aging.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.
Yan
Y
Zhang
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering-Cell Biology, University Hospital of the RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Jan
J
Hapala
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.|Network Aging Research (NAR), University of Heidelberg, Bergheimer Strasse 20, 69120 Heidelberg, Germany.
Hermann
H
Brenner
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering-Cell Biology, University Hospital of the RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Wolfgang
0000-0002-1971-3217
W
Wagner
D000375:Aging / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D006801:Humans; D008017:Life Expectancy
D005819:Genetic Markers
Aging; DNA methylation; Epigenetic; Life expectancy; Mortality; Predictor