Research Article: Epigenetic-aging-signature to determine age in different tissues

Date Published: October 26, 2011

Publisher: Impact Journals LLC

Author(s): Carmen M. Koch, Wolfgang Wagner.

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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.

Partial Text

Aging has different consequences in different tissues – it results for example in wrinkle formation of dermis, graying of epidermally-derived hair, loss of bone formation, myeloid bias of blood, and compromised function of the immune system [1]. Despite this wide spectrum of tissue specific age-associated changes the underlying molecular mechanisms might be related. Aging has been associated with accumulation of cellular defects such as DNA damage and telomere shortening. On the other hand, there is accumulating evidence that aging rather resembles a developmentally regulated process which is tightly controlled by specific epigenetic modifications [2-8].

In this study we have identified an Epigenetic-Aging-Signature consisting of five CpG sites which facilitates predictions of donor age across different tissue types. This method can for example be used in forensic analysis to estimate donor age of unknown tissue specimen including blood. It has to be noted, that chronological age is not identical with biological age and it is conceivable that some of the discrepancy between predicted and real age can be attributed to this difference – further research might facilitate determination of the biological age for personalized medicine.

 

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