DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

Mar 2, 2016Aging

DNA methylation at specific age-related sites may indicate life expectancy

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Abstract

A five-year higher age-prediction from a 99-CpG aging model is associated with 11% greater mortality risk.

Differences between epigenetic age-predictions and chronological age may indicate all-cause mortality risk.
Models using three CpGs or individual CpGs show significant inaccuracies when tested on independent datasets.
DNAm levels at certain individual age-associated CpGs are associated with life expectancy.
Specific genes, such as PDE4C and CLCN6, show potential links to biological aging markers.
Small aging signatures may require more precise quantitative analysis methods for accurate age predictions.

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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.

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DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

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