Age estimation using DNA methylation technique in forensics: a systematic review

Background: In addition to the DNA sequence, epigenetic markers have become substantial forensic tools during the last decade. Estimating the age of an individual from human biological remains may provide information for a forensic investigation. Age estimation in molecular strategies can be obtained by telomere length, mRNa mutation, or by sjTRECs but the accuracy is not sufficient in forensic practice because of high margin error. Main body: One solution to this problem is to use DNA methylation methods. DNA methylation markers for tissue identification at age-associated CpG sites have been suggested as the most informative biomarkers for estimating the age of an unknown donor. This review aims to give an overview of DNA methylation profiling for estimating the age in cases of forensic relevance and the important aspects in determining the mean absolute deviation (MAD) or mean absolute error (MAE) of the estimated age. Online database searching was performed through PubMed, Scopus, and Google Scholar with keywords selected for forensic age estimation. Thirty-two studies were included in the review, with variable DNA samples but blood commonly as a source. Pyrosequencing and EpiTYPER were methods mostly used in DNA analysis. The MAD in the estimates from DNA methylation was about 3 to 5 years, which was better than other methods such as those based on telomere length or signal-joint T-cell receptor excision circles. The ELOVL2 gene was a commonly used DNA methylation marker in age estimation. Conclusion: DNA methylation is a favorable candidate for estimating the age at the time of death in forensic profiling, with an uncertainty mean absolute deviation of about 3 to 5 years in the predicted age. The sample type, platform techniques used, and methods to construct age predictive models were important in determining the accuracy in mean absolute deviation or mean absolute error. The DNA methylation outcome suggests good potential to support conventional STR profiling in forensic cases.