Abstract
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.
Highlights
Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition affecting 7% of the US population[1]
Because cell type proportions have been implicated in whole blood DNA methylation (DNAm) and RNA-Seq data analysis, the proportions of CD8 and CD4 T cells, natural killer cells, B cells, and monocytes were previously estimated in these samples based on Houseman et al
Our results suggested that World Trade Center (WTC) responders with current PTSD had evidence of accelerated transcriptional aging compared to WTC responders who did not have PTSD
Summary
Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition affecting 7% of the US population[1]. It is associated with reduced lifespan and healthspan, suggesting accelerated aging[2,3]. Newer DNAm age calculators have since emerged, aiming to optimize the prediction of phenotypic age according to clinical attributes associated with mortality and morbidity. These include PhenoAge[16] and GrimAge[17], which seek to improve the prediction of age-related outcomes, e.g., time to death and time to diagnosis for cancer, Alzheimer’s disease and cardiovascular disease
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