Epigenetic-aging-signature to determine age in different tissues

Abstract

All tissues of the organism are affected by aging. This process is associated with epigenetic modifications such as methylation changes at specific cytosine residues in the DNA (CpG sites). Here, we have identified an Epigenetic-Aging-Signature which is applicable for many tissues to predict donor age. DNA-methylation profiles of various cell types were retrieved from public data depositories - all using the HumanMethylation27 BeadChip platform which represents 27,578 CpG sites. Five datasets from dermis, epidermis, cervical smear, T-cells and monocytes were used for Pavlidis Template Matching to identify 19 CpG sites that are continuously hypermethylated upon aging (R > 0.6; p-value <10−13). Four of these CpG sites (associated with the genes NPTX2, TRIM58, GRIA2 and KCNQ1DN) and an additional hypomethylated CpG site (BIRC4BP) were implemented in a model to predict donor age. This Epigenetic-Aging-Signature was tested on a validation group of eight independent datasets corresponding to several cell types from different tissues. Overall, the five CpG sites revealed age-associated DNA-methylation changes in all tissues. The average absolute difference between predicted and real chronological age was about 11 years. This method can be used to predict donor age in various cell preparations - for example in forensic analysis.

A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects

“…Tel: +1 8048283428; Fax: +1 8046283991; Email: jlmcclay@vcu.edu genome-wide. As a step in this direction, several recent studies have used the Illumina Infinium 27 K microarray to investigate age-related methylation effects in fibroblasts (15), cultured human cells (16), buccal DNA (17), whole blood (18)(19)(20)(21) and concordance of age-related change across multiple tissue types (22). To date, two studies on aging have also employed the higher density Infinium 450 K array (23,24).…”

Distinctive topology of age-associated epigenetic drift in the human interactome

“…Indeed, a meta-analysis of age-associated DNAm changes in human tissue, focusing primarily on blood and brain tissue, concluded that many age-associated changes are common to both tissue types (33). Moreover, in contrast to gene expression and copy number, consistency of age-associated DNAm signatures has been high, and for instance, it has been possible to build remarkably accurate DNAm-based predictors of age (34)(35)(36).…”

In Silico Approaches and the Role of Ontologies in Aging Research

“…These epigenetic modifications may be used to track donor age for forensic analysis or for estimation of biological age. 16 In his talk on ''Age-Associated DNA-Methylation Changes are Reversed in Pluripotent Stem Cells,'' Wolfgang Wagner (RWTH Aachen) reported on such age-related DNAm (ARDNAm) changes identified from more than 500 DNAm profiles from blood. These AR-DNAm changes were further 544 FUELLEN ET AL.…”