Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
Department of Family and Preventive Medicine, Stony Book University, Stony Brook, NY, USA.
Transl Psychiatry. 2021 May 24;11(1):311. doi: 10.1038/s41398-021-01437-0.
Posttraumatic stress disorder (PTSD) is associated with shortened lifespan and healthspan, which suggests accelerated aging. Emerging evidence suggests that methylation age may be accelerated in PTSD. It is important to examine whether transcriptional age is also accelerated because transcriptome is highly dynamic, associated with age-related outcomes, and may offer greater insight into the premature aging in PTSD. This study is the first reported investigation of the relationship between transcriptional age and PTSD. Using RNA-Seq data from our previous study on 324 World Trade Center responders (201 never had PTSD, 81 with current PTSD, and 42 with past PTSD), as well as a transcriptional age calculator (RNAAgeCalc) recently developed by our group, we found that responders with current PTSD, compared with responders without a PTSD diagnosis, showed accelerated transcriptional aging (p = 0.0077) after adjustment for chronological age and race. We compared our results to the epigenetic aging results computed from several epigenetic clock calculators on matching DNA methylation data. GrimAge methylation age acceleration was also associated with PTSD diagnosis (p = 0.0097), and the results remained significant after adjustment for the proportions of immune cell types. PhenoAge, Hannum, and Horvath methylation age acceleration were not reliably related to PTSD. Both epigenetic and transcriptional aging may provide biological insights into the mechanisms underpinning aging in PTSD.
创伤后应激障碍（PTSD）与寿命和健康寿命缩短有关，这表明存在加速老化。新出现的证据表明，PTSD 患者的甲基化年龄可能会加速。重要的是要检查转录年龄是否也会加速，因为转录组非常动态，与与年龄相关的结果相关，并且可能更深入地了解 PTSD 中的过早衰老。本研究是首次报道转录年龄与 PTSD 之间的关系。我们使用了来自我们之前对 324 名世界贸易中心救援人员（201 名从未患有 PTSD，81 名患有当前 PTSD，42 名患有过去 PTSD）的 RNA-Seq 数据，以及我们小组最近开发的转录年龄计算器（RNAAgeCalc），发现与没有 PTSD 诊断的救援人员相比，当前患有 PTSD 的救援人员在调整了年龄和种族后，表现出转录年龄加速（p=0.0077）。我们将我们的结果与从匹配的 DNA 甲基化数据计算得出的几个表观遗传时钟计算器的表观遗传衰老结果进行了比较。GrimAge 甲基化年龄加速也与 PTSD 诊断相关（p=0.0097），并且在调整免疫细胞类型比例后，结果仍然显著。PhenoAge、Hannum 和 Horvath 甲基化年龄加速与 PTSD 没有可靠的关系。表观遗传和转录衰老都可能为 PTSD 中衰老的机制提供生物学见解。
