From the time we're born to the time we die, a lot may change, but our DNA-the long, double-helix molecule that contains all of a person's genetic code-stays the same. The instructions for reading that code can shift, however, as the chemical tags on and around a DNA sequence change throughout our lives, depending on our age, environment, and behavior. This outside influence on how our genes are read and expressed by cells is called epigenetics-and researchers studying it have discovered clues that may show why some veterans live longer than others.
Scientists can interpret epigenetic changes and patterns by looking at DNA methylation (DNAm), a process that turns a gene "on" or "off." (For example, smokers tend to have reduced DNAm in a gene shown to have a role in suppressing tumors, making them more susceptible to disease.) DNAm can also indicate a person's cellular age, which can be different from their numerical age, and point to risk factors associated with early death.
In a new study of military veterans published in Translational Psychiatry, researchers discovered a connection between DNAm signals of accelerated cellular aging and mental health conditions like post-traumatic stress disorder (PTSD)-findings that suggest former service personnel with PTSD are at greater risk of early death.
"Our study found that PTSD and comorbid conditions, like substance misuse, are associated with a cellular marker of early death found in DNA methylation patterns," says Erika Wolf, a Boston University Chobanian & Avedisian School of Medicine professor of psychiatry and senior author on the study. An early death is one that occurs before the average age of death, which in the United States is about 75 years, but differs slightly between men and women.
The study included two samples of veterans that had representative levels of trauma and other psychiatric conditions, like substance use and personality disorders. One group included 434 veterans in their early 30s, who had served in post-9/11 conflicts; the other group included 647 middle-age veterans and their trauma-exposed spouses. Both groups were assessed for a range of psychological conditions, and had blood drawn to obtain genetic information and to test for levels of a variety of inflammatory molecules.
The data was then put into an existing algorithm called GrimAge-which is designed to predict time to death based on methylation data in a person's blood and other types of biomarkers-and correlated with a range of psychiatric diagnoses, biomarkers, cognitive tests, and brain morphology. The researchers also accounted for the influence of age.
According to the paper, the veterans' DNAm index of time to death was associated with a number of adverse clinical outcomes, including high inflammation levels, oxidative stress, alterations in immune and metabolic molecules, and cognitive decline. The results indicated PTSD symptoms were a factor in faster cellular aging-.36 of a year faster, according to Wolf. So, for every year that the cells of someone without PTSD age, the cells of someone with more severe PTSD symptoms age a year and a third.
The study is the first to detect associations between a broad range of trauma-related psychiatric symptoms and some of the earliest warning signs of mortality risk via DNAm patterns. But Wolf, a clinical research psychologist for the National Center for PTSD at the VA Boston Healthcare System, says that a person's fate is not set in stone and there are ways to avoid the risk of early death. She says the research has important clinical implications, since lifestyle interventions may reverse metrics of biological aging and mitigate premature death.
"Collectively, our findings suggest that a number of psychiatric disorders may increase risk for early death and underscore the importance of identification of those at greatest risk," Wolf says.
The algorithm isn't designed to predict a single person's time of death-if people are worried about their biological health, they're much better off getting a metabolic panel, says Wolf-but can help identify biological pathways associated with accelerated aging in broader groups. For example, if we know about a particular inflammatory process that is problematic among those with accelerated cellular aging, then scientists can work to develop something to correct that.
"We know of some health behaviors that reduce inflammation, like exercise and stress reduction, good nutrition," Wolf says. "The ability to detect low levels of these molecules years before they may become clinically significant, and hopefully be able to intervene early on in disease trajectories, is critical for efforts to ultimately slow or reverse the adverse health consequences of traumatic stress."
Funding for this study was provided by the US Department of Veterans Affairs, the National Institutes of Health, and the National Institute of Mental Health.
