title: DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy.
abstract: DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy - e.g., at CpGs associated with the genesPDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH University Medical School, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH University Medical School, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Carola I
authors.initials: CI
authors.lastname: Weidner
authors.affiliation: Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.|Interdisciplinary Centre for Clinical Research (IZKF), RWTH University Medical School, Aachen, Germany.
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Costa
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.|Queensland Brain Institute, The University of Queensland, Brisbane 4072, QLD, Australia.
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.|Interdisciplinary Centre for Clinical Research (IZKF), RWTH University Medical School, Aachen, Germany.|Department of Statistics, Centre for Natural and Exact Sciences, Federal University of Paraiba, CEP 58051-900, João Pessoa, Brazil.
authors.forename: Marcelo R P
authors.initials: MR
authors.lastname: Ferreira
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.|Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH University Medical School, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D006801:Humans; D008017:Life Expectancy; D008297:Male; D016016:Proportional Hazards Models
keywords: CLCN6; DNA-methylation; PDE4C; age; aging; epigenetic; mortality; prediction; predictor; survival