Accelerated extrinsic epigenetic aging and increased natural killer cells in blood of suicide completers

Background: Studies suggest aberrant DNA methylation in victims of suicide. Recently, DNA methylation profiles have been developed for determining "epigenetic age," which is the most accurate estimate of biological age. Subsequently, two refined measures of epigenetic age acceleration have been expanded for blood samples as intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively). IEAA involves pure epigenetic aging independent of blood cell composition, whereas EEAA involves immunosenescence in association with blood cell composition. Methods: We investigated epigenetic age acceleration using two independent DNA methylation datasets: a brain dataset from 16 suicide completers and 15 non-psychiatric controls and a blood dataset compiled using economical DNA pooling technique from 56 suicide completers and 60 living healthy controls. In the blood dataset, we considered IEAA and EEAA, as well as DNA methylation-based blood cell composition. Results: There was no significant difference in universal epigenetic age acceleration between suicide completers and controls in both brain and blood datasets. Blood of suicide completers exhibited an increase in EEAA, but not in IEAA. We additionally found that suicide completers had more natural killer cells but fewer granulocytes compared to controls. Conclusion: This study provides novel evidence for accelerated extrinsic epigenetic aging in suicide completers and for the potential application of natural killer cells as a biomarker for suicidal behavior.