Verhoeven Josine E, Yang Ruoting, Wolkowitz Owen M, Bersani Francesco S, Lindqvist Daniel, Mellon Synthia H, Yehuda Rachel, Flory Janine D, Lin Jue, Abu-Amara Duna, Makotkine Iouri, Marmar Charles, Jett Marti, Hammamieh Rasha
Department of Psychiatry, UCSF Weill Institute for Neuroscience, University of California San Francisco, School of Medicine, San Francisco, California, USA.
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Mol Neuropsychiatry. 2018 Oct;4(2):90-99. doi: 10.1159/000491431. Epub 2018 Sep 5.
DNA methylation patterns change with age and can be used to derive an estimate of "epigenetic age," an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variables in 160 male combat-exposed war veterans with ( = 79) and without PTSD ( = 81). DNA methylation was assessed in leukocyte genomic DNA using the Illumina 450K DNA methylation arrays. Epigenetic age was estimated using Horvath's epigenetic clock algorithm and Δage (epigenetic age-chronological age) was calculated. In veterans with PTSD (Δage = 3.2), Δage was on average lower compared to those without PTSD (Δage = 5.0; = 0.02; Cohen's d = 0.42). This between-group difference was not explained by race/ethnicity, lifestyle factors or childhood trauma. Antidepressant use, however, explained part of the association. In the PTSD positive group, telomerase activity was negatively related to Δage (β = -0.35; = 0.007). In conclusion, veterans with PTSD had significantly lower epigenetic age profiles than those without PTSD. Further, current antidepressant use and higher telomerase activity were related to relatively less epigenetic aging in veterans with PTSD, speculative of a mechanistic pathway that might attenuate biological aging-related processes in the context of PTSD.
DNA甲基化模式随年龄变化，可用于推算“表观遗传年龄”，这是生物年龄的一个指标。多项研究表明，创伤后应激障碍（PTSD）与较差的躯体健康状况和过早死亡有关，这增加了生物衰老加速的可能性。本研究调查了160名有过战斗经历的男性退伍军人（其中79人患有PTSD，81人未患PTSD）的估计表观遗传年龄与各种变量之间的关联。使用Illumina 450K DNA甲基化芯片评估白细胞基因组DNA中的DNA甲基化。使用Horvath的表观遗传时钟算法估算表观遗传年龄，并计算Δ年龄（表观遗传年龄-实际年龄）。在患有PTSD的退伍军人中（Δ年龄 = 3.2），与未患PTSD的退伍军人相比（Δ年龄 = 5.0；p = 0.02；Cohen's d = 0.42），平均Δ年龄更低。种族/民族、生活方式因素或童年创伤并不能解释这种组间差异。然而，使用抗抑郁药可以部分解释这种关联。在PTSD阳性组中，端粒酶活性与Δ年龄呈负相关（β = -0.35；p = 0.007）。总之，患有PTSD的退伍军人的表观遗传年龄特征显著低于未患PTSD的退伍军人。此外，目前使用抗抑郁药和较高的端粒酶活性与患有PTSD的退伍军人相对较少的表观遗传衰老有关，推测这是一条可能在PTSD背景下减弱生物衰老相关过程的机制途径。
