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Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans

  • Amanda J.F. Tamman
    Correspondence
    Send correspondence and reprint requests to Amanda J.F. Tamman, Ph.D., Baylor College of Medicine, 1177 Butler Blvd., Houston, TX 77030.
    Affiliations
    Department of Psychiatry, Baylor College of Medicine (AJFT), Houston, TX
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  • Sheila Nagamatsu
    Affiliations
    Department of Psychiatry, Yale School of Medicine (SN, JHK, JG, JLM-O, RHP), New Haven, CT
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  • John H. Krystal
    Affiliations
    Department of Psychiatry, Yale School of Medicine (SN, JHK, JG, JLM-O, RHP), New Haven, CT

    U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System (JHK, JG, RHP), West Haven, CT
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  • Joel Gelernter
    Affiliations
    Department of Psychiatry, Yale School of Medicine (SN, JHK, JG, JLM-O, RHP), New Haven, CT

    U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System (JHK, JG, RHP), West Haven, CT
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  • Janitza L. Montalvo-Ortiz
    Affiliations
    Department of Psychiatry, Yale School of Medicine (SN, JHK, JG, JLM-O, RHP), New Haven, CT
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  • Robert H. Pietrzak
    Affiliations
    Department of Psychiatry, Yale School of Medicine (SN, JHK, JG, JLM-O, RHP), New Haven, CT

    U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System (JHK, JG, RHP), West Haven, CT

    Department of Social and Behavioral Sciences, Yale School of Public Health (RHP), New Haven, CT
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Published:September 09, 2022DOI:https://doi.org/10.1016/j.jagp.2022.09.002

      Highlights

      • What is the primary question addressed by this study?
        We aimed to examine a broad range of psychosocial correlates of accelerated GrimAge, a “mortality clock” algorithm comprised of DNA methylation surrogates of plasma proteins and smoking pack-years that is associated with various morbidities and time-to-death.
      • What is the main finding of this study?
        About 18.3% of veterans had five or more years of accelerated GrimAge. Fewer days of physical exercise per week, history of lifetime substance use disorder, greater number of lifetime potentially traumatic events, lower gratitude, reduced sleep quality, lower openness to experience, and unmarried/partnered status were independently associated with greater odds of accelerated GrimAge.
      • What is the meaning of the finding?
        Given potential modifiability of many of these factors, findings may inform precision medicine-based targets for interventions to mitigate veterans' risk for premature mortality.

      Abstract

      Objective

      Veterans are at high risk for health morbidities linked to premature mortality. Recently developed “epigenetic clock” algorithms, which compute intra-individual differences between biological and chronological aging, can help inform prediction of accelerated biological aging and mortality risk. To date, however, scarce research has examined potentially modifiable correlates of GrimAge, a novel epigenetic clock comprised of DNA methylation surrogates of plasma proteins and smoking pack-years associated with various morbidities and time-to-death. The objective of the study was to examine psychosocial correlates of this novel epigenetic clock.

      Design

      Cross-sectional study.

      Setting

      U.S. veteran population.

      Participants

      Participants were male, European American (EA), and derived from a nationally representative sample of U.S. veterans (N = 1,135, mean age = 63.3, standard deviation [SD] = 13.0).

      Measurements

      We examined the prevalence of accelerated GrimAge and its association with a broad range of health, lifestyle, and psychosocial variables.

      Results

      A total 18.3% of veterans had accelerated GrimAge (≥5 years greater GrimAge than chronological age; mean = 8.4 years acceleration, SD = 2.2). Fewer days of weekly physical exercise (relative variance explained [RVE] = 27%), history of lifetime substance use disorder (RVE = 21%), greater number of lifetime traumas (RVE = 19%), lower gratitude (RVE = 13%), reduced sleep quality (RVE = 7%), lower openness to experience (RVE = 7%), and unmarried/partnered status (RVE = 6%) were independently associated with increased odds of accelerated GrimAge. Increasing numbers of these risk factors were associated with greater odds of accelerated GrimAge, with greatest likelihood of acceleration for veterans with ≥3 risk factors (weighted 21.5%).

      Conclusions

      These results suggest that nearly 1-of-5 EA male U.S. veterans have accelerated GrimAge, and highlight a broad range of health, lifestyle, and psychosocial variables associated with accelerated GrimAge. Given that many of these factors are modifiable, these findings provide promising leads for risk stratification models of accelerated biological aging and precision medicine-based targets for interventions to mitigate risk for premature mortality in this population.

      Key Words

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      Linked Article

      • Psychosocial Determinants of Biological Aging in Older Adults: What is Next?
        The American Journal of Geriatric Psychiatry
        • Preview
          Aging is a highly heterogenous process and a major risk factor for a myriad of adverse health outcomes. A major quest in biomedical research is the search for metrics (i.e., biological aging measures) that can provide a more accurate information about our aging process, reducing the sample heterogeneity, predicting adverse health outcomes, and informing biological mechanisms of aging.1 Among many biological aging measures, the epigenetic clocks based on specific patterns of DNA methylation have become popular measures of biological aging.
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