Application of array-based age prediction models to post-mortem tissue samples

Abstract

Since DNA methylation at specific CpG sites exhibits a strong age association, researchers have developed numerous age prediction models based on the methylation BeadChip array. These models harness epigenetic clocks that hold the potential to narrow down the search range for unknown suspects and unidentified victims. This study collected 180 post-mortem tissue samples comprising nine tissue types (blood, brain, heart, lung, liver, kidney, muscle, epidermis, and dermis) from autopsies of 20 Koreans aged 18-78. Subsequently, DNA methylation profiling was conducted using the Infinium MethylationEPIC array. We tested several array-based age prediction models using the data obtained from various tissues. The pan-tissue clock exhibited a moderately accurate prediction across all nine tissue types (MAE = 8.7 years, r = 0.88). Notably, the DNAm ages of the Hannum clock, the skin & blood clock, and the Zhang clock strongly correlated with the actual age in blood samples (MAE < approximately 5 years, r > 0.9). PhenoAge yielded an MAE of 10.1 years and an r-value of 0.92. The muscle-specific epigenetic clock, the MEAT package, demonstrated high prediction accuracy in muscle samples (MAE = 4.7 years, r = 0.93). Those previously reported array-based age prediction models were mainly constructed in Europeans but performed well in Koreans. In addition, tests involving various quantities of DNA and fragmented DNA have shown that DNA quantity and quality affected methylation measurements and age prediction results. However, robust age prediction models exist under low amounts of DNA and fragmented DNA conditions.

Keywords: Age prediction; DNA methylation; Deconvolution; Epigenetic clock; Post-mortem tissue.