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自杀既遂者血液中外在表观遗传衰老加速和自然杀伤细胞增加。

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

机构信息

Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.

Division of Legal Medicine, Department of Community Medicine and Social Health Science, Kobe University Graduate School of Medicine, Kobe, Japan.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 2;98:109805. doi: 10.1016/j.pnpbp.2019.109805. Epub 2019 Nov 7.

Abstract

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.

摘要

背景

研究表明自杀者存在异常的 DNA 甲基化。最近,已经开发出用于确定“表观遗传年龄”的 DNA 甲基化图谱,这是对生物年龄最准确的估计。随后,两种用于血液样本的更精确的表观遗传年龄加速测量方法——内在和外在表观遗传年龄加速(IEAA 和 EEAA)得到了扩展。IEAA 涉及与血细胞成分无关的纯表观遗传衰老,而 EEAA 涉及与血细胞成分相关的免疫衰老。

方法

我们使用两个独立的 DNA 甲基化数据集来研究表观遗传年龄加速:一个是来自 16 名自杀完成者和 15 名非精神病对照者的大脑数据集,另一个是使用经济的 DNA 池化技术从 56 名自杀完成者和 60 名健康对照者中编译的血液数据集。在血液数据集中,我们考虑了 IEAA 和 EEAA ,以及基于 DNA 甲基化的血细胞成分。

结果

在大脑和血液数据集中,自杀完成者和对照组之间普遍的表观遗传年龄加速没有显著差异。自杀完成者的血液中 EEAA 增加,但 IEAA 没有增加。我们还发现,与对照组相比,自杀完成者的自然杀伤细胞更多,而粒细胞更少。

结论

这项研究为自杀完成者的外在表观遗传加速提供了新的证据,并为自然杀伤细胞作为自杀行为的潜在生物标志物提供了应用前景。

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